The Evolution of Research Techniques in Premature Infant Nutrition
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Nutrition of the Low Birthweight Infant, edited by B. L. Salle and P. R. Swyer. Nestle Nutrition Workshop Series, Vol. 32. Nestec Ltd., Vevey/Raven Press, Ltd., New York © 1993. The Evolution of Research Techniques in Premature Infant Nutrition Buford L. Nichols, Jr. USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital, Houston, Texas 77030, USA THE RISE OF THE TECHNOLOGY OF PREMATURE INFANT CARE Tarnier, the French obstetrician, developed an incubator for premature infant care after seeing young chickens in an incubator at the Paris Zoo in 1878. The premature infant incubator was demonstrated in a series of technologic exhibits at World's Fairs and Expositions between 1897 and 1932. When the incubators were demonstrated for the public, premature infants were used in the display; although the drama of the presentation appealed to the general public, it appalled the medical community. Louise Recht, the nurse who managed the incubators, had been trained by Budin and used a variety of techniques to feed the infants. She demonstrated Tarnier's method of intragastric gavage and Monti's method of feeding with nasal spoons. The milk fed to the infants had usually been donated (1,2). In 1929, Pirquet, surveying the hospital management of premature infants, stated, "the main difficulty encountered in the rearing of premature children is primarily a nutritional one" (3). This chapter reviews the scientific development of premature infant feeding during an era when premature infants were placed on exhibition. I shall focus on the methods used to determine the nutritional needs of premature infants. THE ORIGINS OF NUTRITIONAL SCIENCE In the fifth century, Hippocrates is believed to have said, "Growing bodies have the most innate heat; they therefore require the most food, for otherwise, their bodies are wasted." This quotation from the age of antiquity sets the stage for the work of the 17th century Belgian iatrochemist Van Helmont, who used the chemical methods of his day to study problems of health. The 18th century English discoveries of carbon dioxide by Black in 1757, oxygen by Priestley in 1774, and the development of animal calorimetry by Crawford in 1779 provided the foundation for the brilliant work of Lavoisier. In 1777, Lavoisier confirmed Priestley's experimental finding that oxygen 31 32 EVOLUTION OF RESEARCH TECHNIQUES was exhausted by respiration if a sparrow were placed in a bell jar. The process was identical to that associated with the oxidation of metals. Using an ice calorimeter, Lavoisier measured the quantity of heat produced by the combustion of carbon into CO2. He continued these studies of carbon oxidation in guinea pigs and humans. After collecting gas in a closed system filled with water and inverted over a water bath, Lavoisier measured the volume of air caught and added phosphorus metal. The burning of the metal completely used up the oxygen, after which potash was intro- duced to remove the carbon dioxide. The remaining gas was analyzed by differences in the water level after treatment (4). The fourth century recognition of the primary elements of air, earth, fire, and water presaged the concept that air was important to life processes (4). This concept met with skepticism from Van Helmont, who combined chemistry with medicine (as had Paracelsus) and began the development of nutrition science as we know it. He coined the word "gas." In the early 18th century Stephen Hales of England included a chapter on "Analysis of Air" in his book Vegetable Statistics. Hales invented a "pedestal apparatus" bell jar to show for the first time that air became "fixed" by many organic and inorganic materials. The School of Pneumatic Chemists in England based much of its research on the work of Hales and flourished in its use of the "pedestal apparatus." In 1756, Joseph Black, one of Hales' disciples, discovered that "fixed air" or carbon dioxide was present in the mineral dolomite. Pneumatic chemistry, an area of study guided by Robert Boyle, contributed the physical laws governing the properties of gas and the discovery of "inflammable air" or hydrogen by Cavendish in 1766. Joseph Priestley described the "different kinds of air" and reported his discovery of "respirable air" or oxygen in 1772 (5). Hales' pedestal apparatus was modified by the French chemist Rouelle to allow the collection of gases. Using the technique, gases were generated in a distillation flask and the volume was estimated by the drop of the water level in the bell jar. Lavoisier used Hales' apparatus to measure the interaction of both inorganic and organic material with the volume of air to show that gases play a quantitative role in chemical reactions. He thus became the first to grasp the significance of air to chemical transformations. He used a gravimetric balance to demonstrate weight gain during the oxidation of phosphorus or sulfur and weight loss when metal oxides were reduced by high temperatures provided by a giant magnifying glass. Lavoisier observed changes in gas volume that correlated quantitatively with altered mass. His discovery of the law of conservation of mass was reported in 1771, after which air was understood to be a chemical participant in life processes (5). Lavoisier then turned his attention to the relationship between heat and oxidation. Using the bell jar and a calorimeter constructed with double layers of ice, he showed that when wood or charcoal was burned a quantitative equivalence of carbon and oxygen was consumed and carbon dioxide and heat were produced. This experiment was repeated with a living guinea pig to show that the same quantitative relationship between carbon dioxide and heat production existed in a living mammal. Using the Rouelle modification of Hales' pedestal apparatus, Lavoisier measured oxygen con- sumption and CO2 production in his laboratory assistant, Seguin. Lavoisier's interest EVOLUTION OF RESEARCH TECHNIQUES 33 in quantitation led to his participation in the Commission on Weights and Measures, which resulted in the centimeter-gram system of calibration units. Lavoisier contrib- uted the definition of a calorie as the unit of heat necessary to raise the temperature of one cubic centimeter of water by one degree centigrade. Lavoisier died in 1794, a casualty of the French Revolution (4). The scientific descendants of Lavoisier continued to make elemental gas analyses using an eudiometer. Justus Liebig studied under Lavoisier's student, Gay-Lussac, from whom he learned quantitative chemistry and the endiometric techniques. He returned to his native Germany to use the new methods in animal chemistry or bio- chemistry studies. When Liebig undertook the proximate analysis of animal foods, tissue constituents, and isolated chemical substances using the eudiometer, new in- sights came about in rapid succession. The discovery that nitrogen was a constituent of all living matter opened the way to protein chemistry and the concept of nutrient balance. In France, Boussingault was the first to determine carbon balance in a lactating cow. Liebig carried out a nitrogen balance study in a company of the Ducal Guards in Darmstadt, Germany (4). ENERGY NEEDS An evaluation in France of Lavoisier's theory of calories enabled the concept of food calorie content. In 1849, Regnault and Reiset (6) extended the Hales/Rouelle bell jar experiment in a closed system with a fixed supply of air. They studied the oxygen consumption and CO2 production by a dog. Their "closed system" was used to measure the carbon oxidation of infants in a large bell jar. The Regnault-Reiset apparatus for study of oxygen utilization and CO2 production was modified in 1887 by Langlois (7) in Paris and in 1894 by Mensi in Turin (Table 1). A further evolution of this methodology was reported in France in 1908 by Weiss and in 1914 in the USA by Benedict and Talbot (9,10,17). The calorimetry energy expenditure results were less than estimates derived from studies of energy intakes in term and premature infants. In 1862 Pettenkofer and Voit in Munich developed the "open system" of indirect calorimetry. They designed a room with controlled ventilation in which an experimental subject was placed and CO2 production measured by a gravimetric procedure (18). The equipment was used by Forster (19) in 1877 to determine CO2 production in an infant. The methodology was modified and used in Berlin by Rubner and Langstein (11) in 23-hour calorimetry studies CO2 production by two premature infants at the Kaiserin Victoria Kinder Haus reported in 1915. Rubner criticized the previous work done in the closed system calorimeter because the measurements were of short duration and their emphasis was on basal metabolism rather than total carbon oxidation: "If respiratory investigations are to serve as a measure for the general consumption of nutrients, they must extend for day and night, so that the quantity of respiration corresponds to all functions of the infant" (20). The results were sum- marized by Levine in 1936 and 1940, who concluded that the total amount of heat 34 EVOLUTION OF RESEARCH TECHNIQUES TABLE 1. Daily energy expenditure of premature infants Total Author expenditure Year (location) Apparatus (calories/kg/d) Reference 1887 Langlois (Paris)8 Direct/Regnault-Reiset 81,109 7 1904 Hasselbalch Open/Pettenkofer-Vogt 31 8 (Copenhagen)3 1914 Benedict and Talbot Closed/Benedict 89-103 9,10 (Boston) 1915 Rubner and Langstein Open/Pettenkofer-Vogt 121-130 11 (Berlin) 1925 Marsh and Murlin Closed/Benedict 49 12 (Rochester) 1932 Schadow (Hamburg) Closed 45-54 13 1933 von Schlossman Closed 44-62 14 (Dusseldorf) 1936 Gordon et al. (New Closed/Benedict 58 15 York) 1940 Gordon et al. (New Open/gas analysis 68 16 York) Range 31-130 • Calculated by author from original data. produced by premature infants was lower than the amount of heat produced by term infants (Table 1) (15,16).