Volume 86 Number 6
Letters to the Editor
Reply To the Editor: I am most interested in the work of Dr. Gacs and his colleagues reporting lower blood glucose and free fatty acid levels in infants with congenital heart disease and a right to left shunt. 1 In the relatively few babies in whom I had an opportunity to estimate FFA levels after the immediate neonatal period I had the impression that the phenomenon of poor elevation described in hypoxemic babies was confined to the first week of life. There were too few babies to draw any firm conclusions, and I feel that Dr. Gacs' work adds important new knowledge to the problems of lipolysis in the infant. It would seem that in the first week of life there is a basic defect in lipolysis, glycogenolysis, and gluconeogenesis in certain groups of hypoxemic babies. There are good correlates in the animal work of Baum and associates,2,3 who demonstrated that acute hypoxia prevented both cold-stimulated and epinephrine-induced lipolysis in puppies. It may be that we are seeing a similar reaction in hypoxemic, term infants, and in infants with cyanotic congenital heart disease. What is now required is a full evaluation of the various factors involved in the processes of lipolysis and glycolysis. Gacs has shown normal steroid, insulin, and growth hormone levels in the babies he studied. I would suggest that we need to consider the whole concept of "stress hormones" in the human neonate. In particular, the role of glucagon and catecholamines at this critical period of life need careful evaluation in view of their important place in the regulation of carbohydrate and lipid metabolism. With improved assays now becoming available, one can look forward to much stimulating and fruitful research.
R. J. Harris The London Hospital Whitechapel, London E11BB England REFERENCES 1. Gacs G, Kun E, and Berend K: Hypoglycaemia in infants and children with cyanotic congenital heart disease, Acta Paediatr Acad Sci Hung 14:105, 1973. 2. Baum D, Anthony CL, and Stowers C: Impairment of cold stimulated lipolysis by acute hypoxia, Am J Dis Child 121:115, 1971. 3. Baum D: The inhibition of norepinephrine--stimulated lipolysis in acute hypoxia, J Pharmacol Exp Ther 169:87, 1969.
Feeding and plasma NEFA levels in newborn infants
found lower blood glucose level and surprisingly lower plasma NEFA in SGA babies than in term babies. In previous studies 2, 3 NEFA levels had been found to be higher in SGA than in term infants. Harris speculated that the major factors accounting for his results were the early and adequate feeding together with the fact that his babies were kept warm. We have also worked on the same subject and our results are rather different. In a study of the pathogenesis of hypoglycemia in SGA babies we measured urinary catecholamine excretion, blood glucose, and plasma NEFA levels during the ten first days of life in 22 SGA, seven preterm, and five term babies. 4 The neonatal period was uncomplicated, except for laeriod of hypoglycemia between the third and fifth day of life in 12 SGA babies. All babies were kept at environmental temperatures appropriate for their weight and maturity. 5 Plasma NEFA levels were higher in SGA than in the term infants during the first two days of life (p (0.01); between the third and fourth to fifth day hypoglycemic SGA babies maintained higher NEFA levels than did nonhypoglycemic SGA but even the later had higher plasma NEFA than did term babies. The only methodologic difference between the study of Harris and ours was the way SGA babies were fed. In our study SGA and term babies were fed in the same way: glucose in water feedings were started at six hours of age and breast milk was given beginning at 12 hr at a rate of 50 ml/kg during the first day which was increased progressively to 150 ml/kg t3y the seventh day. In Harris' study SGA babies were fed within two hours of birth with glucose in water and with breast milk at age eight or 11 hours (70, 110, and 150 ml/kg at Days 1, 2, and 3, respectively). He fed his term newborn infants in the same way as we did, Although glucose administration early in life results in a fall of plasma NEFA, 6 it is uncertain whether minor differences in feeding of SGA babies may explain the discrepancies between our results and those of Harris as far as the plasma level of NEFA in SGA babies is concerned. NEFA levels in neonatal plasma are not only of theoretical but also of clinical interest because of the possible relationship between plasma NEFA and platelet function, 7 and its interaction with plasma albumin (which is important in neonatal jaundice). It therefore appears that the whole subject of the plasma NEFA and its relationship to early feeding merit further investigation.
D. Anagnostakis First Department of Pediatrics Athens University "St. Sophie's" Children's Hospital Athens, 608, Greece REFERENCES 1.
To the Editor: Recently Harris 1 measured blood glucose and plasma nonesterified fatty acid (NEFA) in term, preterm, and small-forgestational-age (SGA) babies within 72 hours after birth and
991
2.
Harris RJ: Plasma nonesterified fatty acid and blood glucose levels in healthy and hypoxemic newborn infants, J PEDIATR84:578, 1974. Melichar V, Novak M, Sabata V, Hahn P, and Koldovsky O: Free fatty acids and glucose in the blood of hypotrophic n e w b o r n s and n e w b o r n s from diabetic
992
3.
4.
5.
6.
7.
Letters to the Editor
mothers. The effect of glucose and glucose + insulin infusions to the mother, Physiol Bohemoslov 14:553, 1965. Gentz JCH, Warner R, Persson BEH, and Cornblath M: Intravenous glucose tolerance, plasma insulin, free fatty acids and/3-hydroxybutyrate in underweight newborn infants, Acta Paediatr Scand 58:481, 1969. Anagnostakis D, and Lardinois R: Urinary catecholamine excretion and plasma NEFA concentration in small for date infants, Pediatrics 47:1000, 1971. Silverman WA, Sinclair JC, and Agate FJ Jr: The oxygen cost of minor changes in heat balance of small newborn infants, Acta Paediatr Scand 55,294, 1966. Novak M, Melichar V, Hahn P, and Koldovsky O: Levels of lipids in the blood of newborn infants and the effect of glucose administration, Physiol Bohemoslov 10:488, 1961. Hoak JC, Spector AA, Fry GL, and Warner ED: Effect of free fatty acids on ADP induced platelet aggregation, Nature 228:1330, 1970.
Reply To the Editor: It is not too surprising that Dr. Anagnostakis and I should report differing results in our respective groups of SGA babies, since plasma NEFA levels are subject to so many external influences that comparable conditions are almost impossible to obtain in two separate series. However, Dr. Anagnostakis raises two possible influences which merit further consideration, namely temperature and nutrition. The role of temperature on the circulating plasma NEFA levels remains contentious. It would seem that our respective thermal environments were similar, and that the difference in our reported results should not be related to this. However, there are conflicting reports in the literature on the importance of temperature on the postnatal elevation of plasma NEFA levels. One report showed no rise in circulating levels in lambs kept warm immediately after birth, 1 whereas another report showed that there was little difference in levels between infants kept warm after birth and those subjected to thermal stress. 2 The nutritional question is, I feel, the most important single factor which may account for our differing results. In an earlier, unreported, group of SGA infants who were not fed as early as those in my reported series, the mean plasma NEFA levels in
The Journal of Pediatrics June I975
the first 24 hours of life were higher than those of healthy term infants. To my knowledge, there are no reports of plasma NEFA levels in SGA infants fed as early and as liberallY as those in my series. By the time Dr. Anagnostakis' babies received their first feed, those in my series had received two and sometimes three feeds. I feel that this supports the view that early administration of glucose causes a fall in plasma NEFA levels. 3 Recently, it has been reported that there is a fall in plasma NEFA between 12 and 24 hours of age in a group of early fed, term infants, 4 which is ascribed to the early adequate calorie intake of these babies. Thus, I would contend that the difference between my results and those of Dr. Anagnostakis rests on a mere four hours--the difference in timing of the first feeds in our two series. In conclusion, I would like to endorse Dr. Anagnostakis' plea for further investigation of the whole subject of plasma NEFA and its relationship to early feeding. In addition, further investigation of the many factors causing lipolysis in the immediate neonatal period is urgently required, in particular the whole field of hormonal influences under differing conditions of temperature and stress. I would also add the plea that when reporting the results of plasma NEFA levels in early neonatal life, that authors also report in detail temperature conditions and nutritional status. Roger J. Harris The London Hospital Whitechapel, London El lBB England REFERENCES 1. Alexander G, and Mills SC: Free fatty acids and glucose in the plasma of newly born lambs, Biol Neonate 13:53, 1968. 2. Persson BEH, and Tunell R: Influence of environmental temperature and acidosis on lipid mobilisation in the h u m a n infant during the first two hours after birth, Acta Paediatr Scand 60:385, 1971. 3. Novak M, Melichar V, Hahn P, and Koldovsky O: Levels of lipids in the blood of newborn infants and the effect of glucose administration, Physiol Bohemoslov 10:488, 1961. 4. Christensen N: Lipids in cord serum and free fatty acids in plasma in healthy newborn term infants, Acta Paediatr Scand 63:711, 1974.
Letters to the Editor
Reply To the Editor: I am most interested in the work of Dr. Gacs and his colleagues reporting lower blood glucose and free fatty acid levels in infants with congenital heart disease and a right to left shunt. 1 In the relatively few babies in whom I had an opportunity to estimate FFA levels after the immediate neonatal period I had the impression that the phenomenon of poor elevation described in hypoxemic babies was confined to the first week of life. There were too few babies to draw any firm conclusions, and I feel that Dr. Gacs' work adds important new knowledge to the problems of lipolysis in the infant. It would seem that in the first week of life there is a basic defect in lipolysis, glycogenolysis, and gluconeogenesis in certain groups of hypoxemic babies. There are good correlates in the animal work of Baum and associates,2,3 who demonstrated that acute hypoxia prevented both cold-stimulated and epinephrine-induced lipolysis in puppies. It may be that we are seeing a similar reaction in hypoxemic, term infants, and in infants with cyanotic congenital heart disease. What is now required is a full evaluation of the various factors involved in the processes of lipolysis and glycolysis. Gacs has shown normal steroid, insulin, and growth hormone levels in the babies he studied. I would suggest that we need to consider the whole concept of "stress hormones" in the human neonate. In particular, the role of glucagon and catecholamines at this critical period of life need careful evaluation in view of their important place in the regulation of carbohydrate and lipid metabolism. With improved assays now becoming available, one can look forward to much stimulating and fruitful research.
R. J. Harris The London Hospital Whitechapel, London E11BB England REFERENCES 1. Gacs G, Kun E, and Berend K: Hypoglycaemia in infants and children with cyanotic congenital heart disease, Acta Paediatr Acad Sci Hung 14:105, 1973. 2. Baum D, Anthony CL, and Stowers C: Impairment of cold stimulated lipolysis by acute hypoxia, Am J Dis Child 121:115, 1971. 3. Baum D: The inhibition of norepinephrine--stimulated lipolysis in acute hypoxia, J Pharmacol Exp Ther 169:87, 1969.
Feeding and plasma NEFA levels in newborn infants
found lower blood glucose level and surprisingly lower plasma NEFA in SGA babies than in term babies. In previous studies 2, 3 NEFA levels had been found to be higher in SGA than in term infants. Harris speculated that the major factors accounting for his results were the early and adequate feeding together with the fact that his babies were kept warm. We have also worked on the same subject and our results are rather different. In a study of the pathogenesis of hypoglycemia in SGA babies we measured urinary catecholamine excretion, blood glucose, and plasma NEFA levels during the ten first days of life in 22 SGA, seven preterm, and five term babies. 4 The neonatal period was uncomplicated, except for laeriod of hypoglycemia between the third and fifth day of life in 12 SGA babies. All babies were kept at environmental temperatures appropriate for their weight and maturity. 5 Plasma NEFA levels were higher in SGA than in the term infants during the first two days of life (p (0.01); between the third and fourth to fifth day hypoglycemic SGA babies maintained higher NEFA levels than did nonhypoglycemic SGA but even the later had higher plasma NEFA than did term babies. The only methodologic difference between the study of Harris and ours was the way SGA babies were fed. In our study SGA and term babies were fed in the same way: glucose in water feedings were started at six hours of age and breast milk was given beginning at 12 hr at a rate of 50 ml/kg during the first day which was increased progressively to 150 ml/kg t3y the seventh day. In Harris' study SGA babies were fed within two hours of birth with glucose in water and with breast milk at age eight or 11 hours (70, 110, and 150 ml/kg at Days 1, 2, and 3, respectively). He fed his term newborn infants in the same way as we did, Although glucose administration early in life results in a fall of plasma NEFA, 6 it is uncertain whether minor differences in feeding of SGA babies may explain the discrepancies between our results and those of Harris as far as the plasma level of NEFA in SGA babies is concerned. NEFA levels in neonatal plasma are not only of theoretical but also of clinical interest because of the possible relationship between plasma NEFA and platelet function, 7 and its interaction with plasma albumin (which is important in neonatal jaundice). It therefore appears that the whole subject of the plasma NEFA and its relationship to early feeding merit further investigation.
D. Anagnostakis First Department of Pediatrics Athens University "St. Sophie's" Children's Hospital Athens, 608, Greece REFERENCES 1.
To the Editor: Recently Harris 1 measured blood glucose and plasma nonesterified fatty acid (NEFA) in term, preterm, and small-forgestational-age (SGA) babies within 72 hours after birth and
991
2.
Harris RJ: Plasma nonesterified fatty acid and blood glucose levels in healthy and hypoxemic newborn infants, J PEDIATR84:578, 1974. Melichar V, Novak M, Sabata V, Hahn P, and Koldovsky O: Free fatty acids and glucose in the blood of hypotrophic n e w b o r n s and n e w b o r n s from diabetic
992
3.
4.
5.
6.
7.
Letters to the Editor
mothers. The effect of glucose and glucose + insulin infusions to the mother, Physiol Bohemoslov 14:553, 1965. Gentz JCH, Warner R, Persson BEH, and Cornblath M: Intravenous glucose tolerance, plasma insulin, free fatty acids and/3-hydroxybutyrate in underweight newborn infants, Acta Paediatr Scand 58:481, 1969. Anagnostakis D, and Lardinois R: Urinary catecholamine excretion and plasma NEFA concentration in small for date infants, Pediatrics 47:1000, 1971. Silverman WA, Sinclair JC, and Agate FJ Jr: The oxygen cost of minor changes in heat balance of small newborn infants, Acta Paediatr Scand 55,294, 1966. Novak M, Melichar V, Hahn P, and Koldovsky O: Levels of lipids in the blood of newborn infants and the effect of glucose administration, Physiol Bohemoslov 10:488, 1961. Hoak JC, Spector AA, Fry GL, and Warner ED: Effect of free fatty acids on ADP induced platelet aggregation, Nature 228:1330, 1970.
Reply To the Editor: It is not too surprising that Dr. Anagnostakis and I should report differing results in our respective groups of SGA babies, since plasma NEFA levels are subject to so many external influences that comparable conditions are almost impossible to obtain in two separate series. However, Dr. Anagnostakis raises two possible influences which merit further consideration, namely temperature and nutrition. The role of temperature on the circulating plasma NEFA levels remains contentious. It would seem that our respective thermal environments were similar, and that the difference in our reported results should not be related to this. However, there are conflicting reports in the literature on the importance of temperature on the postnatal elevation of plasma NEFA levels. One report showed no rise in circulating levels in lambs kept warm immediately after birth, 1 whereas another report showed that there was little difference in levels between infants kept warm after birth and those subjected to thermal stress. 2 The nutritional question is, I feel, the most important single factor which may account for our differing results. In an earlier, unreported, group of SGA infants who were not fed as early as those in my reported series, the mean plasma NEFA levels in
The Journal of Pediatrics June I975
the first 24 hours of life were higher than those of healthy term infants. To my knowledge, there are no reports of plasma NEFA levels in SGA infants fed as early and as liberallY as those in my series. By the time Dr. Anagnostakis' babies received their first feed, those in my series had received two and sometimes three feeds. I feel that this supports the view that early administration of glucose causes a fall in plasma NEFA levels. 3 Recently, it has been reported that there is a fall in plasma NEFA between 12 and 24 hours of age in a group of early fed, term infants, 4 which is ascribed to the early adequate calorie intake of these babies. Thus, I would contend that the difference between my results and those of Dr. Anagnostakis rests on a mere four hours--the difference in timing of the first feeds in our two series. In conclusion, I would like to endorse Dr. Anagnostakis' plea for further investigation of the whole subject of plasma NEFA and its relationship to early feeding. In addition, further investigation of the many factors causing lipolysis in the immediate neonatal period is urgently required, in particular the whole field of hormonal influences under differing conditions of temperature and stress. I would also add the plea that when reporting the results of plasma NEFA levels in early neonatal life, that authors also report in detail temperature conditions and nutritional status. Roger J. Harris The London Hospital Whitechapel, London El lBB England REFERENCES 1. Alexander G, and Mills SC: Free fatty acids and glucose in the plasma of newly born lambs, Biol Neonate 13:53, 1968. 2. Persson BEH, and Tunell R: Influence of environmental temperature and acidosis on lipid mobilisation in the h u m a n infant during the first two hours after birth, Acta Paediatr Scand 60:385, 1971. 3. Novak M, Melichar V, Hahn P, and Koldovsky O: Levels of lipids in the blood of newborn infants and the effect of glucose administration, Physiol Bohemoslov 10:488, 1961. 4. Christensen N: Lipids in cord serum and free fatty acids in plasma in healthy newborn term infants, Acta Paediatr Scand 63:711, 1974.
