Narrator:

Introducing Doctor Nadja Haiden, a pediatrician specializing in neonatology and pediatric intensive care medicine, and a faculty member at the Medical University of Vienna. She is a researcher at the Department of Clinical Pharmacology at the Medical University of Vienna, where she also received her medical education. Professor Haiden has led several high impact research projects which investigate growth and metabolic outcomes in preterm infants following the introduction of complementary feeding. She has authored over 90 peer-reviewed publications. She currently serves as chair of the National Committee on Pediatric Nutrition at the Austrian Pediatric Society, head of the National Neonatal Nutrition Committee of the Federal Ministry of Health, and chair of the Nutrition Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. Please welcome Doctor Haiden.

Dr. Nadja Haiden:

Well, thank you very much for the invitation. It's a great opportunity and the honor to speak in front of such, international pediatric society. So my topic today is the post-discharge management of former preterm infants. And first of all, I'd like to address, my disclosures. And, first, I want to show you the current approaches and the future approaches to optimize, the health outcomes of former preterm infants. And, on the, in the left column, you can see what we are actually often doing. And in the blue column you can see what we should do. And there are also 2 topics related to nutrition. And the one is the timing tailored to individual needs. And the other topic is the aim for health optimization and thriving. And these are topics related to optimal health. Health potential to optimize the long-term outcome of preterm infants. And as already stated, the ESPGHAN published a position paper recently, 6 weeks ago on the assessment of growth status and nutritional management of former preterm infants after hospital discharge to support clinicians, in the long term follow up of these patients. So one of the objectives of my talk. First of all, how should a NICU graduate, grow post-discharge. What is the optimal growth trajectory and growth velocity? One nutritional strategies can support catch up growth in case you need catch up growth. Is there a right time point for the introduction of complementary feeding? And do we need supplements to support preterm infants.

So first of all, what is the optimal way to monitor growth. So for the time before term, we, most of us follow the Fenton growth charts. These, growth charts are designed for preterm infants. And they, support, the monitoring up to 52 weeks. And after the term, the WHO growth charts for breastfed infants are available. And here you can see, on this picture, we can see, a merge of these 2, growth charts. So on the left-hand side, the Fenton growth charts and on the right-hand side, the WHO growth charts for breastfed infants. And what you can see here is that they don't fit together perfectly at term. So the transition between Fenton growth charts, and WHO growth charts is perfect around 44 weeks of gestation. And this is the time point where you should switch, the growth charts to monitor growth, properly. You can see here also the green line. This represents a preterm infant, growing in length, head circumference and weight. And the green line, represents the physiological adjustment after birth in weight and with transition into post discharge in infancy. So what you can see here, the infant is born here with the weight on the 50th percentile. Then it has a drop of -1 SD and it, crosses again the percentile of the birth percentile around 44 weeks, when you switch from Fenton to, WHO growth charts. In addition, what are the best parameters to monitor your growth? So for sure, we know that weight, length, and head circumference are standard growth parameters. But after term, we have 2 additional parameters that are very helpful to monitor growth, especially in preterm infants. And these are length and weight-for-length sets course. What is a z-score? A z-score describes how many standard deviation a data point is from the mean. So you have, for example, the mean birth weight. And if you have a plus of 2 z-scores, this means that the birth weight has a standard deviation, of +2 from the mean or of the same is on the opposite.

And -2 and -2 represent the third and the 97th percentile. Just to give you a short overview on this. Why is weight for length and, length sets course so important in the monitoring of preterm infants. So when you discharge your preterm infants, usually you have or often you have appropriate weight, but you fall behind in length and head circumference. This is related to a very rapid, weight gain in the early postnatal period. We induce this, with a lot of calories. Sometimes we are very short in protein. And this might cause that the infant gains weight but falls short in length and head circumference. Wise length and head circumference. Important. Well, these 2 parameters are related, to, normal or a proper neurological outcome, much more than weight gain. So, we don't want the infant only to gain weight, we also want them to grow because, this is an increase or represents an increase in fat free mass and is associated with a better long term neurological outcome. And, on the other hand, we know that a rapid weight gain, in early childhood or after discharge is increased within, associated with an increased body fat mass. And this is again associated with a later insulin resistance, a metabolic syndrome, and a higher risk for diabetes, cardiovascular diseases and other non-communicable diseases. So preterm infants, already have a higher risk, to suffer from these diseases later in life and by a very rapid weight gain after discharge, without improving the length of an infant.

You can abbreviate these conditions. So, what is the management now? After discharge, you can see here on this timeline the time from birth to discharge. And the question is, what are our long-term growth targets? And do our infants need nutritional support, extra macron micronutrients. After discharge. And now you have we have to distinguish between if the infant is, born appropriate for gestational age or if the infant is already growth restricted at birth. If the infant is born with an adequate nutritional status and grows appropriately in the initial and is discharged within - or + 2 SDs. This infant is growing appropriately and needs no extra nutritional support. The growth target for the infants born with an adequate nutritional status is always birth percentile - 1 SD. So this is the growth target. And if your infant if it has a complicated course in the neonatal intensive care unit and falls in growth just on the -2 SD or well below, -2 SD, these infants need close monitoring and no extra nutritional support by Macron micronutrients until they catch up growth to their birth percentile -1 SD. The other group of patients who were much more risk for, growth failure are the ones that are already born with growth restriction. In this group of patients our growth target is the physiological percentile -1 SD. And this represents the third percentile. So again, if we have an infant a preterm infants born already with the growth restriction, and this infant grows properly in the intensive care unit and is discharged over -2 SD. This infant needs no extra nutritional support, just monitoring. If you're just under -2 SD or well below -2 SD, ketchup growth again is required. But now, in contrast to the adequately born, infants in this group, we want the infant to grow within their physiological percentile m-1 SD. So we want them to grow into the third percentile. So this is the difference in growth targets between these 2 groups. And this is very important for long-term metabolic programing. What are the infants that are high risk for growth faltering. Well, of course, these are the infants that have a complicated growth in the neonatal intensive care unit, a complicated course that is suffering from bronchopulmonary dysplasia, that was suffering from NEC, that experienced feeding difficulties, vomiting, that had surgical conditions, chromosomal anomalies and that already grow poorly in, the neonatal intensive care unit. So these are the infants that need close monitoring, after discharge up during the first years of life.

So what is the best, nutritional support for, our infants? Of course, you know, that breast is best, we have already heard, about this, but, when it comes to preterm infants, breast milk is even more than nutrition, it's more medication. In this group of patients, we have several beneficial health outcome. When the infant is fed with mother's own milk during their early neonatal period up until discharge. So for example, we have a reduction in sepsis. We have a reduction in necrotizing enterocolitis retinopathy of prematurity branch pulmonary dysplasia. So all these diseases are reduced when you feed breast milk.

And we also have an effect on long term outcome of preterm infants. We have a lower risk for later cardiovascular disease in young adulthood. And we have even an impact on intelligence and neurodevelopment and outcome. We know that infants benefit from breast milk in terms of 7 to 10 points in the assessments for any neurodevelopment assessments, for example, in the Bayley Scales. So breast milk has an enormous effect on, preterm infants. And even after discharge, breast milk is favorable. You can see here data from 2 large preterm birth cohorts to epi page and a lift cohort. These are 2005 thousand former preterm infants that will follow up to school age. And what you can see here in this first graph is the weight, length and head circumference, z scores, between breastfed and or breast milk fed and formula fed infants.

What you can see here that in both, preterm cohorts, the breastfed infants, which are represented by the black lines group, better, than the formula fed infants. So, breastfeeding has an impact on growth. And we also call this the breastfeeding production because, the calories are of course lower than in the formulas. But breast milk is, is a very complex, favorable fluid for preterm infants. And therefore, growth is better and even the neurological outcomes better. You can see here the assessment, with the Kaufman assessment, neurodevelopmental test at 5 years and the relation to breast milk intake. And you can see here the non-breastfed babies that were never, breast fed and mothers breast milk have the lower intelligence scores. And the more breast milk was the longer breast milk was fed. The better outcome neurodevelopmental outcome was assessed in these infants. So the longer breast milk is given as a dose time response, longer breast milk is given, the greater the effect on neurodevelopmental outcome is. What the other have. Do we have other possibilities, to offer enhanced nutrients or higher, richer macro interaction nutrients. But you can see here, the needs for very low birth weight infants and, the critical Macro and micronutrients, here on the left-hand side. And what breast milk offers freedom formula offers or starter formula offers. And for the post-discharge period breast milk with at least 50% fortification or post-discharge formula cover the needs of the preterm infants very satisfactorily.

We have other nutritional options to enrich breast milk or other nutrients or other formulas in case we need to catch up on growth. So we have, on the one hand, human look for indication we have preterm or post discharge formula depending what is available in your country. Post-discharge formula, preterm formula are not available everywhere for the post discharge management. So often they are only available in the hospital. So we can also use standard formula and increase the energy and density with protein and energy models. And we can also use hyper caloric formula for term instance. Please consider that it's very important. To make a sufficient and to care for the protein energy ratio. This is very important to absorb and digest 1 gram of protein, you need at least 30 kilocalories and 0.3 million mol phosphorus. So without adding calories to protein and phosphorus, you won't grow. So the protein energy ratio is very, very important if you enrich, formula with, energy and protein models and therefore the help of a dietitian, is also, very, very helpful and should be considered, when you, manage these, these kind of infants. So what about the introduction of complementary feeding? We know for with these recommended for term infants, we've already addressed this yesterday to introduce complementary feeding between the 17th and 26th week, of life for preterm infants. We have only very limited data, mainly from observational studies. And these studies were showing that usually complementary feeding is introduced very, very early to preterm infants, 13 to 15 weeks of life and corrected age so very, very early. And the degree of prematurity is a major determinant for introduced if we're introducing complementary food. Because the younger the infant is the earlier usually complementary feeding is introduced because we want to cover the nutrients, data from randomized controlled trials are also limited. And we only actually have 4 available investigating different time points and the outcome on growth in preterm infant.

And the key message is the time point of introduction of complementary food does not affect growth in preterm infant. Therefore, it's important to wait for the neuro-methodical readiness of preterm infants. It's much more important, to wait for major, or minor, gross motor skills, for example, that the infant can sit in an upright position that the infant has lip, tongue and jaw movements to accept the spoon and the food. And also, we have to wait, or we should wait for the disappearance of the diminishing reflexes that protect the infant from choking and aspiration, for example, the protrusion of reflex of the tongue. So the neuro-material readiness, is important for the implementation of complementary feeding. And we shouldn't be afraid that the baby won't grow otherwise. The time point of introduction of complementary food does not affect growth in that extension. That we expected. We have also here options.

Now if we need ketchup growth to enhance nutritional density, we can again use models, to enhance energy and nutrient supply. For example, adding maltodextrin or, specific oils. We can use dietary strategies again with the help of a dietitian.

We should also, take care of the textures of, we offer in complementary food to preterm infants because a lot of preterm infants have feeding difficulties and have problems to accept. Textures. So texture is a real important issue in the introduction of complementary feeding. Finally, the supplements, preterm infants do need supplements. Here, data for vitamin D status, in former preterm infants from 6 weeks on to 5 years. And what you can see here, although preterm infants were supplemented during the whole first year, almost more than 80% developed vitamin D deficiency, at 1 year. And this persists up to 5 years. So vitamin D deficiency is a real problem in preterm infants, they need a lot of vitamin D.

And these data showed that supplementing during the first year only in the first year with 650 units per day, is not enough to protect them, from vitamin D deficiency. So vitamin D deficiency is a real problem. Therefore, it is recommended to supplement vitamin D, during the first year of life and over the first winter, with a maximum of 1000 units, per day. And to screen, the high-risk infants and the high-risk infants, in the preterm group are the ones with bronchopulmonary dysplasia that were the very, very immature ones that were on long, parental nutrition. So these infants should be screened, during the first year of life for vitamin D deficiency. The second supplement that is very important is iron. We can detect, iron signs of iron deficiency even in very young preterm infants, even before term, by showing abnormal neurological reflexes with 37 weeks of gestation already when they are iron deficient, they show poor growth, they show gastrointestinal disturbances. They are susceptible for infections, and they are temperature in stable. And we have also later signs of, iron deficiency, showing up by poor behavioral and neurodevelopmental outcome.

And we have even structural changes in the brain, we can find structural changes, morphological strangers in the hippocampus and striatum, in iron deficient infants. And these are, again, data of parameters of iron status from preterm infants, up from, in the post-discharge period up to 5 years. And what you can see here, although they were supplemented, with 2 to 3mg/kg per day until complementary feeding was, induced, approximately 60% of the infants were suffering from early iron deficiency.

Most of them are recovered when complementary feeding was introduced, but still during their childhood approximately 15% where deficient of the former preterm infants. So iron deficiency is not that topic like vitamin D deficiency in preterm infants, but it's still a topic. And we should monitor the high-risk infants in this context. So iron supplement, we should supplement, preterm infants with iron in a dosage of 2 to 3mg/kg per day, at a minimum, up to complementary feeding is introduced. And also the low-birth-weight infants that are not that immature, will benefit from iron supplementation in early childhood. So to conclude, the post-discharge management, of former preterm infant depends very much on the growth status at birth. Remember, it depends if you are appropriate upon appropriate for gestational age or already with the growth regulation, the growth target for infants with appropriate for gestational age is -1 SD to their birth percentile. The growth target for growth already growth restricted infants is -2 SD from their physiological percentile. We have various option to enhance nutritional density in this group of patients.

With formula and complementary feeding. The time point of complementary feeding does not have an impact on growth. And therefore the introduction in preterm infants should be related to their neurological readiness much more than to their corrected age. And finally, preterm infants are highly susceptible for vitamin for late vitamin D deficiency and early iron deficiency and therefore monitoring and supplementation is highly recommended.

Therefore, I would thank you. This is the speaker nutrition committee, my friends and experts, colleagues, that helped me to, to write this position paper and together with them, I thank you for your attention. Thank you.