Optimizing nutrition and growth of very low birth weight (VLBW) infants in order to improve neurodevelopmental outcome and minimize the risk for the developmental onset of adult diseases, mainly metabolic, cardiovascular and neurologic ones (DOHaD)(four studies)
(a) It is well established that breast milk provides the best basis for nutrition of preterm babies due to it containing many “good” substances like antibodies, growth factors, etc. However, the amount of macronutrients like proteins, calories, etc. is often not sufficient and therefore, needs to be fortified. Current standard fortification does not correct or take into account the individual variation for the composition of breast milk. We, therefore, developed a concept to individually fortify breast milk on the basis of the measured macronutrient content (IFO study). We have managed to establish the infrastructure and have completed the first pilot trial that shows that this concept is feasible in a clinical environment. Our initial data indicates that it is safe and will improve postnatal growth in these babies. To perform this pilot study, we developed a new method to determine lactose in breast milk using one of our new mass spectrometers. The results of this study have recently been published in an international peer-reviewed journal. In addition, we have established micromethods to use as little breast milk as possible for lab analysis since it is a very valuable substance for preemies. We are now able to measure all macronutrients using a milk volume of 1.4mL instead of needing 30 to 100mL which was used in prior methods. We have further evaluated commercially available milk analyzers and could show that these devices which have been developed for use in the dairy industry need revisions of their algorithm to obtain valid results for human milk. This study has lead to three publications over the summer with two more to be submitted soon. We also started a double-blind randomized controlled clinical trial in November 2012 for which we have now received funding ($ 472,000) from the Canadian Institute of Health Research (CIHR). We were ranked #1 of 56 applications in this competition. Also, in the meantime the manuscript of the pilot trial has been accepted by Journal of Pediatrics for publication.
The IFO study goes in line with two other studies in which we investigate further aspects of postnatal growth of preterm infants:
(b) the “PEAPOD study” aims to establish longitudinal body composition reference data for stable preterm infants using bedside methods, such as the PEA POD, a device using air displacement plethysmography. Currently, weight, length and head circumference are used as surrogate parameters to indicate nutritional status and somatic growth of the infant and clinical decisions of nutritional adjustment are usually made on these parameters. However, body composition data with detailed measurements of fat and lean mass is critical as it provides a better indication of infant nutritional status compared to simple anthropometric data alone. There is now growing evidence that an unfavourable body composition will affect adult health and predispose to metabolic, neurological and cardiovascular disease. We therefore feel the need to improve the infants’neurodevelopment and outcomes – with special respect to understand better metabolic programming which will have an upcoming role in adjusting nutrition to achieve healthy growth patterns in extremely preterm infants. In order to do this, detailed longitudinal reference data of fat and muscle mass is required. We have composed a multi-disciplinary team, including physicians, research fellows, a study coordinator and a Master’s student who are responsible for the organization of this project.
So far we were able to measure postnatal body composition in more than 60 preterm infants on more than 180 occasions down to 30 weeks of gestation. Due to a recent technical development that we have introduced, evaluated and validated we will now be able to include also infants on intravenous support. This will allow us to expand the age range towards less mature infants (target 27 weeks of gestation) as well as perform measurements in preterm infants earlier after birth (target day 1 of life). We are not aware that any research group has done such early measurements before.
c) the GroWTH study aims to establish longitudinal weight data during the first 14 and 21 postnatal days in healthy preterm infants from 31 to 36 weeks of gestation. “Healthy” has been defined by a panel of exclusion criteria such that these infants had only minimal or no intensive care support and thus represent the healthiest 10% of all infants of a given gestational age. The postnatal weight trajectory of these subjects will be plotted into the intrauterine growth charts; and this “new postnatal” percentile will be considered as the “most golden” standard that indicates where preterm infants most probably will have to adjust to after completed postnatal adaptation. These infants shall therefore be taken as the role model of healthy postnatal growth. So far, we have included more than 570 preterm infants in this study, and a total of more than 5500 preterm infants have been screened so far for eligibility. In order to recruit a significant number of subjects for this study we have managed to establish collaborations with other centres: St Joe’s in Hamilton, St. Mike’s in Toronto, Children’s Hospital University of Heidelberg as well Children’s Hospital University of Greifswald. Preliminary results indicate that the infants adjust on average to -0.74 z-scores across all gestational ages and that the “new” postnatal trajectory can be reliably predicted just from gestational age and birth weight (r2 of 0.95). In a next step we will validate the model and will also try to expand it to gestational ages below 31 weeks of gestation, ideally down to 24 weeks. With the result of this study we will be able to give clinicians for the first time an answer to the question of to which intrauterine percentile postnatal growth an individual infant should be adjusted to.
(d) In the “Lipid Study” we aim to better understand the impact and contribution of parenteral lipid administration on postnatal growth. The two other macronutrients, carbohydrates and proteins, have been extensively studied by the scientific community in the past and major developments have been made and led to advanced commercially available i.v-solutions. Similar research is missing for
lipid emulsions and currently less fat is tolerated by the i.v-route compared to enteral intake. We re currently comparing profiles of fatty acids between different commercially available products (Canada and other countries) and we also investigate fatty acid profiles that are achieved under different nutritional regimes (parenteral vs. enteral). We aim to achieve a better tolerance of i.v. lipids emulsion.