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Early neurological delopment, growth and nutrition in very preterm infants
Maas, Y.G.H.
Publication date
1999
Link to publication
Citation for published version (APA):
Maas, Y. G. H. (1999). Early neurological delopment, growth and nutrition in very preterm
infants.
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Summary
Millions of babies and young infants throughout the world suffer from malnutrition. It is still the most important public health problem in underdeveloped countries. In the early years of life - from gestation onwards - the brain is developing rapidly. During this so called brain growth spurt the neurological system is particularly vulnerable to any growth-restricting events. Malnutrition - surely in its severe form - must cause lasting effects on the developing neurological system, impairing irreversibly full development of the natural abilities and talents of so many infants, provided that they survive. Until now research in this field - relating nutrient depletion and its effects on neurological development in early life - reached a deadlock because of social, psychological, physical and environmental interference with the outcome. The importance of nutrition for immature and critically ill infants and the impact on clinical outcome and neurological development also became a concern for neonatologists in the Western World with the availability of neonatal intensive care units in the 1970s. Consequently, the need for diagnostic tools to assess neurological development of young infants at risk for long-term neurological abnormalities was
reinforced. This research aimed at the discovery of such (a) test(s). Moreover, the effect of nutritional intake on growth and neurological development in very preterm infants were studied and compared. To conclude, the predictive value of the two neurological assessment methods studied in this thesis were compared with the predictive value of two standard neurological tests used in neonatology based on neurodevelopmental outcome at 2 years of corrected age.
In chapter 1 some background information is given on how this thesis came about. Then the state of the art on the three areas studied and combined in this thesis, viz. nutrition, growth and neurological development in very preterm infants (< 30 weeks' gestational age) is presented. The aim of the research is twofold: 1. development of a (clinical) instrument to monitor neurological development and predict long-term outcome of very preterm infants and 2. to test this instrument for its suitability to judge optimality of
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nutrition. The contents of the chapters 2 to 8 are reviewed.
The study design, the study population and the methods used are described in chapter 2. The framework of the study and the restrictive conditions of an interfering randomized thyroxine supplementation trail are briefly mentioned. Of the methods applied in more than two of the chapters 3 to 7 a detailed description is given. For ease of survey a flowchart of the babies participating in the various parts of the research protocol is included in this chapter.
Chapter 3 describes the macronutrient composition of longitudinally collected human milk samples of very preterm infant mothers and deals with the question whether the changes in composition found in these samples are related to the postnatal or postconceptional age of the infant or to the duration of gestation. The 24-hour milk volume was used as a time-varying covariate in the statistical analysis. Postnatal age was clearly related with total nitrogen and lactose content in very preterm milk. While total nitrogen concentration decreased with postnatal age, lactose concentration increased. Only for carbohydrate concentration a gestational age related difference was found: the concentration decreased with an increasing gestational age. No evidence was found for a 'teleological' basis for the patterns of changes in composition for any of the nutrients studied, meaning that the macronutrient composition of human milk is not determined by endogenously generated maturational processes from conception onwards. No relation was found between the amount of 24-hour milk produced and postnatal or gestational age.
Chapter 4 deals with the issue of nutrition and physical development (growth). Early postnatal growth of very preterm infants ( < 30 weeks gestation) was studied on a
longitudinal basis using extensive anthropometry (10 parameters). The infants studied were randomly assigned to start enteral feeding with maternal milk supplemented with standard formula (STF) or preterm formula (PTF) on an isocaloric basis. They were also enrolled in a placebo controlled (double-blind), randomized trial on thyroxine supplementation. Data of postnatal week 1 to 7 were analysed. Preterm formula given as a supplement to maternal milk resulted in an increased overall physical development compared to standard formula supplementation. Additional increase in growth was seen when thyroxine was added to preterm formula supplementation, specifically for head circumference, subscapular and triceps skinfold thickness. Provided that rapid growth is most desirable for very preterm
infants in the early postnatal phase, this study indicates that these infants do benefit from special, adapted formula feeding. Moreover supplementation of thyroxine in combination with preterm formula in the first weeks of life seemed to further increase physical growth. The chapters 5 and 6 study neurological development in very preterm infants (gestation < 30 weeks) in search of an early diagnostic tool to identify babies at risk for longterm neurological disorders. Moreover, both chapters address the subject of a possible relation of nutrition and early neurological development. The infants studied were enrolled in a randomized trial on diet and thyroxine supplementation. Data on the development of behavioural states (e.i. sleep and wakefulness) are presented in chapter 5. The amount of time spent in quiet sleep increased significantly at the expense of the amount of
indeterminate state from 30 to 40 weeks postmenstrual age. This finding confirmed our hypothesis that brain maturation in very preterm infants is reflected in the development of behavioural states when studied postnatally till corrected term age. Based on the covariate analysis indications were found that behavioural states patterns differ amongst normal, mildly abnormal and abnormal (based on cranial ultrasound) infants. Indications were also found for an effect of gender on the development and of weight at birth on the amount of quiet sleep. Both diet and thyroxine supplementation had a significant (interaction) effect on the developmental patterns of behavioural states. However, from stratified analyses we could conclude that neither preterm diet nor thyroxine substantially influence the
developmental course of the amount of time spent in the different behavioural states before term age.
Data on the development of spontaneous motility are provided in chapter 6. The
developmental course of the quality of general movements (GMs) was studied from 30 till 40 weeks (corrected term) age. To this new method has been ascribed high predictive value for assessing neurological outcome when used till 3-4 months post term. That was why we were interested to test its applicability in very preterm infants born before 30 weeks gestation. Quality of GMs was very stable, that is strikingly low, over time before (corrected) term age. No developmental changes in GM quality were seen as a function of postmenstrual age. Moreover, unlike our expectations, the sensitivity and specificity of the GM quality assessment method in relation to outcomes of repeated cranial ultrasound and neurological examination at (corrected) term age are very poor. Indeed recent other studies
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also concluded that assessment of preterm GMs is not highly predictive of later neurological outcome. No effects were found of early diet and/or thyroxine supplementation. From our covariate analysis indications were found for an effect of gender and weight at birth on GM quality.
Though a reliable and easy method to perform, even in a neonatal IC environment, we found assessment of GM quality during the prematurity period (i.e. before corrected term age) to be an unfit method for detecting early neurological disorders or to predict
neurological outcome at term age.
Chapter 7 reports on the predictive value of several neurobehavioural tests easily applicable in a neonatal ICU setting. These tests included: cranial ultrasound, Prechtl neurological test at term, quality of spontaneous general movements and quality of sleep-wake organization. They were tested for their ability to predict the
neurodevelopmental outcome at 2 years of (corrected) age of preterm infants born at a gestational age < 30 weeks. Data on the early neurobehavioural tests were related to the outcome of standardized neurological (Touwen) and psychodevelopmental (Bayley) examination at 2 years of corrected age. The Prechtl neurological test at corrected term age appeared to be the only test able to predict neurological and psychodevelopmental outcomes at 2 years of age independently of the other tests. Cranial ultrasound could not add to the predictive power of the term Prechtl test, however as a stand-alone test it seemed to identify the clearly abnormal infants as well as the Prechtl score. Neurobehavioural tests like repeated cranial ultrasound, quality of general movements and development of sleep are of disappointingly limited value for the prediction of neurodevelopmental abnormality at 2 years' corrected age of preterm infants.
In chapter 8 the results of chapters 3 to 7 are combined in a general discussion. Applicability of the studied methods for research on possible relations between undernourishment and neurological development in very young infants is deliberated. Implications of our findings for new studies are reviewed and a suggestion for future research is given.
In summary our main conclusions are that macronutrient composition of very preterm human milk is not related to the developmental stage of the prematurely born infant, but
rather to the duration of lactation. Physical development or growth reflects dietary intake very well and differences in dietary intake are traceable using longitudinal anthropometry. Longitudinal scoring of behavioural states in preterm infants till corrected term age provides us with a method for measuring brain maturation as opposed to longitudinal scoring of the quality of general movements. The introduction of a "neurological growth curve" accompanying the physical growth curve would improve the assessment of early nutrition. Neither the level of behavioural states organization nor the quality of general movements nor repeated cranial ultrasound when applied till term age yield very reliable tests for prediction of neurological and psychodevelopmental outcomes (at 2 years corrected age) of very preterm infants. We believe that it is likely that the neurological and
psychodevelopmental tests used here do not capture all neurological abnormalities. Organization of behavioural states and quality of general movements both represent basic functions of the brain and therefore they can be expected to be better tests when searching for damage to the CNS. New techniques, like (fjMRI, can be of help in discovering their applicability as predictive tests.
