- Email: [email protected]
Hypertriglyceridemia in infants with bronchopulmonary dysplasia
458
9.
10. 11.
12.
Clinical and laboratory observations
Basic Doppler echocardiography. Clin Diagn Ultrasound 1986;17:7-23. Battacharji SK, Hutchinson EC, McCall AJ. The circle of Willis: the incidence of developmental abnormalities in normal and infarcted brains. Brain 1967;90:747-58. Fields WS, Bruetman ME, Weibel J. Collateral circulation of the brain. Monogr Surg Sci 1965~2:183-259. Schumacher RE, Barks JDE, Johnston MV, et al. Right-sided brain lesions in infants following extracorporeal membrane oxygenation. Pediatrics 1988;82:155-61. Rajn TNK, Kim SY, Meller JL, Srinivasan G, Ghai V, Reyes H. The circle of Willis blood velocity and flow direction after common carotid artery ligation for neonatal ECMO. Pediatrics (in press).
The Journal of Pediatrics March 1989
13. McCormick WF. Vascular disorders of the nervous tissue: anomalies, malformations, and aneurysms. In: Bourne GH, ed. The structure and function of nervous tissue; vol 3. New York: Academic Press, 1969:537-96. 14. Riggs HE, Griffiths JO. Anomalies of the circle of Willis in persons with nervous and mental disorders. Arch Neurol Psychiatry 1938;39:1353-6. 15. Allcock JM. Aneurysms. In: Newton TH, Ports DG, eds. Angiography; book 4. St. Louis: CV Mosby, 1974:2435-40. (Newton TH, Potts DG eds. Radiology of the skull and brain; vol 2.)
Hypertriglyceridemia in infants with bronchopulmonary dysplasia John A. W a r e h a m , MD, Jerry J. Ferlauto, MD, David H. Wells, MD, a n d Robert W. Newell, MD From the Department of Neonatology, Greenville Memorial Hospital, Greenville, South Carolina
Hypertriglyceridemia has been described in preterm infants receiving intravenous lipid emulsions. 1-4Two recent articles 5,6 described preterm infants with elevated serum triglyceride levels during enteral feedings. W e report two cases of preterm infants with severe bronchopulmonary dysplasia in whom profound H T G developed while they were receiving formula feedings. CASE REPORTS
The course of disease in each of our two infants with severe BPD is summarized in the Table. Respiratory support in both was guided by capillary blood gas Values and pulse oximetry, with the Fios being adjusted to keep the oxygen saturation at 90% to 95%. Patient ! was ventilator dependent for 69 days, and oxygen therapy was continued after discharge. Patient 2 died at 14 months of age having never been without ventilator support and supplementa ! oxygen. The HTG developed in both infants during continuous nasojejunal feedings with Similac 24 Special Care formula (Ross Laboratories, Columbus, Ohio) enriched to 30 kcal/oz with a commercial9 preparation of carbohydrate (Polycose) and safflower oil in patient 1, and with Polycose and a commercial preparation
of dietary fat (MCT Oil) in patient 2. Numerous formula changes and a week of peripheral parenteral alimentation without lipids were unsuccessful in lowering the serum TG levels in patient 1; the TG levels fell with time and clinical improvement. No dietary changes based on the TG levels were attempted in patient 2, Caloric intake was consistently miantained at 100 or more kcal/kg/day in both infants, with patient 1 growing well and patient 2 poorly. Both infants were exposed to numerous medications (Table). Neither family history suggested familial hyperlipidemia. BPD Fio~ HTG TG
Bronchopulmonary dysplasia Fraction of inspired oxygen Hype~triglyceridemia Triglyceride
METHODS
The T G values were determined colorimetrically (Ektachem chemistry slide system, Kodak Co., Rochester, N.Y.). Samples were drawn randomly while the infants were clinically stable and well oxygenated. DISCUSSION
Submitted for publication June 27, 1988; accepted Oct. 11, 1988. Reprint requests: John A. Wareham, MD, Department of Neonatology, Children's Hospital, 701 Grove Rd., Greenville, SC 29605,
Ritthamel-Weinstein and Haugen 5 described a premature infant with BPD and a mild elevation in serum T G levels while being given enteral feedings with standard
Volume 114 Number 3
Clinical and laboratory observations
459
Table. Patient summaries Birth Gestational Age at Patient weight age diagnosis Clinical status No. (kg) (wk) (mo) at diagnosis
Medications at diagnosis
Range of TG values (mg/dl)
1
1.6
33
41A
BPD GE reflux Ventilator dependent Fio2 = 0.29
Furosemide 352-2142 (4.0-24.1 Gentamicin mmol/L) Theophylline Chloral hydrate Hydrochlorothiazide Prednisone Terbutaline aerosols Spironolactone
2
1.1
29
5
BPD GE reflux Ventilator dependent Fio2 = 0.43
Furosemide 452-1152 (5.1-13 Theophylline mmol/L) Cromolyn Simethicone Hydrochlorothiazide Chloral hydrate Terbutaline aerosols Spironolactone
Additional laboratory values Cholesterol: peak = 326 mg/dl (8.4 mmol/L) FFA: peak = 1.067 mEq/L 3'-GTP: peak = 250 IU/L (4.17 tzkat/L) ALT: peak = 69 IU/L (1.2 ~kat/L) Cholesterol:239 mg/dl (6.2 mmol/L) FFA: 0.15 mEq/L ALT: peak = 69 IU/L (1.2 ~zkat/L)
GE, Gastroesophageal;FFA, free fatty acids;"y-GTP, 3,-gtutamyltranspeptidase;ALT, alaninetransaminase(SGPT).
premature formulas. The serum TG levels had been in the normal range during intravenous lipid infusions of up to 2 gm/kg/day. Greer et al. 6 reported a number of healthy preterm infants with elevations in serum TG levels after discharge on a regimen of human milk feedings. The same infants had had normal TG levels while taking human milk in the hospital. A control group of premature infants fed 20 kcal/oz formula maintained essentially normal TG levels after discharge. Our two infants are similar clinically to the patient described by Ritthamel-Weinstein an d Haugen2 As in both of the preceding reports, our two infants maintained normal serum TG levels while receiving lipids intravenously. The cause of this HTG during enteral feedings is unclear. It may be related to the increase in the percentage of lipid calories associated with the change to enteral feedings. However, that would not explain the difference between the formula-fed and human milk-fed groups in the study by Greer et al.,6 because the fat concentration in the 20 kcal/oz formula is similar to the values reported for their samples of human milk. Deficiencies of lipoprotein lipase or its cofactor apoprotein CII have been postulated as reasons for lipid intolerance in premature and small-for-gestational-age infants,2,3,7 but that hypothesis is controversial.4,s,9 The role of hepatic lipase is also unclear?,911 Medications may play a role; infants with BPD are usually exposed to numerous medications. Theophylline, sympathomimetic drugs, and thiazide diuretics can alter
lipid metabolism and were used in our infants for prolonged periods. The significance of the H T G in our infants is unknown. It is of concern to have chronically high TG levels in infants with BPD because of previous articles linking HTG with impaired oxygenation,12 and intravenous lipid infusions with fat deposition in pulmonary vessels. 13,14Fluctuation in the TG level did not seem to alter the Fi02 requirement significantly in either of the infants, but data for a rigorous comparison are not available. We conclude that HTG during enteral feedings is a problem in certain preterm infants, both well and chronically ill, and that the problem occurs with human milk, standard premature formulas, and calorically enriched premature formulas. More research is needed to define the cause and significance of this observation. REFERENCES
1. Gustafson A, Kjellmer I, Olcgard R, Victorin LH. Nutrition in low birth weight infants. II. Repeated intravenous injections of fat emulsion. Acta Paediatr Stand 1974;63:177-82. 2. Andrew G, Chan G, Schiff D. Lipid metabolism in the neonate. I. The effects of Intralipid infusion on plasma triglyceridc and free fatty acid concentrations in the neonate. J PEDIATR1976;88:273-8. 3. Shennan AT, Bryan MH, Angel A. The effect of gestational age on Intralipid tolerance in newborn infants. J PEDIATR 1977;91:134-7. 4. Dhanircddy R, Hamosh M, Sivasubramian KN, ct al. Postheparin lipolytic activity and Intralipid clearance in very lowbirth-weight infants. J PEDIATR1981;98:617-22. 5. Ritthamel-Weinstein MR, Haugen K. Hypertriglyceridemia
4 60
6.
7.
8.
9.
Clinical and laboratory observations
The Journal of Pediatrics March 1989
in an infant with bronchopulmonary dysplasia. Nutr Clin Pract 1987;2:112-6. Greer FR, McCormick A, Kashyap ML, Glueck EJ. Late hypertriglyceridemia in very low birth weight infants fed human milk exclusively. J PEDIATR1987;111:466-9. Smigura FC, Bryan H, Angel A. Postheparin lipase activity in newborn infants. In: Hahn P, Segal S, Israels S, eds. The role of fat in intravenous feeding of the newborn. Dorval, Quebec; Pharmacia (Canada) Ltd., 1974:129. Rovamo L, Nikkila EA, Taskinen MR, Raivio K. Postheparin plasma lipopr0tein and hepatic lipases in preterm neonates. Pediatr Res 1984;18:1104-7. Lane DM, McConathy WJ. Factors affecting the lipid and apolipoprotein levels of cord sera. Pediatr Res 1983;17:8391.
10. Stahl GE, Spear ML, Hamosh M. Intravenous administration of lipid emulsions to premature infants. Clin Perinatol 1986;13:133-63. 11. Rovamo L, Taskinen MR, Kuusi T, et al. Postheparin plasma lipase activities and plasma lipoproteins in newborn infants. Pediatr Res 1984;18:642. 12. Pereira G, Fox WW, Stanley CA, et al. Decreased oxygenation and hyperlipemia during intravenous fat infusions in premature infants. Pediatrics 1980;66:26-30. 13. Levene MI, Wigglesworth JS, Desai R. Pulmonary fat accumulation after Intralipid infusion in the preterm infant. Lancet 1980;2:815-8. 14. Dahms BB, Halpin TC. Pulmonary arterial lipid deposit in newborn infants receiving intravenous lipid infusion. J PEDIATR 1980;97:800-5.
FELLOWSHIPS Available fellowships in pediatric subspecialties and those for general academic pediatric training are listed once a year, in May, in THE JOURNAL OF PEDIATRICS. Each October, forms for listing such fellowships are sent to the Chairman of the Department of Pediatrics at most major hospitals in the United States and Canada. Should you desire to list fellowships, a separate application must be made each year for each position. All applications must be returned to The C.V. Mosby Company by February 15 of the listing year to ensure publication. Additional forms will be supplied on request from the Journal Editing Department, The C.V. Mosby Company, 11830 Westline Industrial Drive, St. Louis, M O 63146-3318/314-872-8370.
9.
10. 11.
12.
Clinical and laboratory observations
Basic Doppler echocardiography. Clin Diagn Ultrasound 1986;17:7-23. Battacharji SK, Hutchinson EC, McCall AJ. The circle of Willis: the incidence of developmental abnormalities in normal and infarcted brains. Brain 1967;90:747-58. Fields WS, Bruetman ME, Weibel J. Collateral circulation of the brain. Monogr Surg Sci 1965~2:183-259. Schumacher RE, Barks JDE, Johnston MV, et al. Right-sided brain lesions in infants following extracorporeal membrane oxygenation. Pediatrics 1988;82:155-61. Rajn TNK, Kim SY, Meller JL, Srinivasan G, Ghai V, Reyes H. The circle of Willis blood velocity and flow direction after common carotid artery ligation for neonatal ECMO. Pediatrics (in press).
The Journal of Pediatrics March 1989
13. McCormick WF. Vascular disorders of the nervous tissue: anomalies, malformations, and aneurysms. In: Bourne GH, ed. The structure and function of nervous tissue; vol 3. New York: Academic Press, 1969:537-96. 14. Riggs HE, Griffiths JO. Anomalies of the circle of Willis in persons with nervous and mental disorders. Arch Neurol Psychiatry 1938;39:1353-6. 15. Allcock JM. Aneurysms. In: Newton TH, Ports DG, eds. Angiography; book 4. St. Louis: CV Mosby, 1974:2435-40. (Newton TH, Potts DG eds. Radiology of the skull and brain; vol 2.)
Hypertriglyceridemia in infants with bronchopulmonary dysplasia John A. W a r e h a m , MD, Jerry J. Ferlauto, MD, David H. Wells, MD, a n d Robert W. Newell, MD From the Department of Neonatology, Greenville Memorial Hospital, Greenville, South Carolina
Hypertriglyceridemia has been described in preterm infants receiving intravenous lipid emulsions. 1-4Two recent articles 5,6 described preterm infants with elevated serum triglyceride levels during enteral feedings. W e report two cases of preterm infants with severe bronchopulmonary dysplasia in whom profound H T G developed while they were receiving formula feedings. CASE REPORTS
The course of disease in each of our two infants with severe BPD is summarized in the Table. Respiratory support in both was guided by capillary blood gas Values and pulse oximetry, with the Fios being adjusted to keep the oxygen saturation at 90% to 95%. Patient ! was ventilator dependent for 69 days, and oxygen therapy was continued after discharge. Patient 2 died at 14 months of age having never been without ventilator support and supplementa ! oxygen. The HTG developed in both infants during continuous nasojejunal feedings with Similac 24 Special Care formula (Ross Laboratories, Columbus, Ohio) enriched to 30 kcal/oz with a commercial9 preparation of carbohydrate (Polycose) and safflower oil in patient 1, and with Polycose and a commercial preparation
of dietary fat (MCT Oil) in patient 2. Numerous formula changes and a week of peripheral parenteral alimentation without lipids were unsuccessful in lowering the serum TG levels in patient 1; the TG levels fell with time and clinical improvement. No dietary changes based on the TG levels were attempted in patient 2, Caloric intake was consistently miantained at 100 or more kcal/kg/day in both infants, with patient 1 growing well and patient 2 poorly. Both infants were exposed to numerous medications (Table). Neither family history suggested familial hyperlipidemia. BPD Fio~ HTG TG
Bronchopulmonary dysplasia Fraction of inspired oxygen Hype~triglyceridemia Triglyceride
METHODS
The T G values were determined colorimetrically (Ektachem chemistry slide system, Kodak Co., Rochester, N.Y.). Samples were drawn randomly while the infants were clinically stable and well oxygenated. DISCUSSION
Submitted for publication June 27, 1988; accepted Oct. 11, 1988. Reprint requests: John A. Wareham, MD, Department of Neonatology, Children's Hospital, 701 Grove Rd., Greenville, SC 29605,
Ritthamel-Weinstein and Haugen 5 described a premature infant with BPD and a mild elevation in serum T G levels while being given enteral feedings with standard
Volume 114 Number 3
Clinical and laboratory observations
459
Table. Patient summaries Birth Gestational Age at Patient weight age diagnosis Clinical status No. (kg) (wk) (mo) at diagnosis
Medications at diagnosis
Range of TG values (mg/dl)
1
1.6
33
41A
BPD GE reflux Ventilator dependent Fio2 = 0.29
Furosemide 352-2142 (4.0-24.1 Gentamicin mmol/L) Theophylline Chloral hydrate Hydrochlorothiazide Prednisone Terbutaline aerosols Spironolactone
2
1.1
29
5
BPD GE reflux Ventilator dependent Fio2 = 0.43
Furosemide 452-1152 (5.1-13 Theophylline mmol/L) Cromolyn Simethicone Hydrochlorothiazide Chloral hydrate Terbutaline aerosols Spironolactone
Additional laboratory values Cholesterol: peak = 326 mg/dl (8.4 mmol/L) FFA: peak = 1.067 mEq/L 3'-GTP: peak = 250 IU/L (4.17 tzkat/L) ALT: peak = 69 IU/L (1.2 ~kat/L) Cholesterol:239 mg/dl (6.2 mmol/L) FFA: 0.15 mEq/L ALT: peak = 69 IU/L (1.2 ~zkat/L)
GE, Gastroesophageal;FFA, free fatty acids;"y-GTP, 3,-gtutamyltranspeptidase;ALT, alaninetransaminase(SGPT).
premature formulas. The serum TG levels had been in the normal range during intravenous lipid infusions of up to 2 gm/kg/day. Greer et al. 6 reported a number of healthy preterm infants with elevations in serum TG levels after discharge on a regimen of human milk feedings. The same infants had had normal TG levels while taking human milk in the hospital. A control group of premature infants fed 20 kcal/oz formula maintained essentially normal TG levels after discharge. Our two infants are similar clinically to the patient described by Ritthamel-Weinstein an d Haugen2 As in both of the preceding reports, our two infants maintained normal serum TG levels while receiving lipids intravenously. The cause of this HTG during enteral feedings is unclear. It may be related to the increase in the percentage of lipid calories associated with the change to enteral feedings. However, that would not explain the difference between the formula-fed and human milk-fed groups in the study by Greer et al.,6 because the fat concentration in the 20 kcal/oz formula is similar to the values reported for their samples of human milk. Deficiencies of lipoprotein lipase or its cofactor apoprotein CII have been postulated as reasons for lipid intolerance in premature and small-for-gestational-age infants,2,3,7 but that hypothesis is controversial.4,s,9 The role of hepatic lipase is also unclear?,911 Medications may play a role; infants with BPD are usually exposed to numerous medications. Theophylline, sympathomimetic drugs, and thiazide diuretics can alter
lipid metabolism and were used in our infants for prolonged periods. The significance of the H T G in our infants is unknown. It is of concern to have chronically high TG levels in infants with BPD because of previous articles linking HTG with impaired oxygenation,12 and intravenous lipid infusions with fat deposition in pulmonary vessels. 13,14Fluctuation in the TG level did not seem to alter the Fi02 requirement significantly in either of the infants, but data for a rigorous comparison are not available. We conclude that HTG during enteral feedings is a problem in certain preterm infants, both well and chronically ill, and that the problem occurs with human milk, standard premature formulas, and calorically enriched premature formulas. More research is needed to define the cause and significance of this observation. REFERENCES
1. Gustafson A, Kjellmer I, Olcgard R, Victorin LH. Nutrition in low birth weight infants. II. Repeated intravenous injections of fat emulsion. Acta Paediatr Stand 1974;63:177-82. 2. Andrew G, Chan G, Schiff D. Lipid metabolism in the neonate. I. The effects of Intralipid infusion on plasma triglyceridc and free fatty acid concentrations in the neonate. J PEDIATR1976;88:273-8. 3. Shennan AT, Bryan MH, Angel A. The effect of gestational age on Intralipid tolerance in newborn infants. J PEDIATR 1977;91:134-7. 4. Dhanircddy R, Hamosh M, Sivasubramian KN, ct al. Postheparin lipolytic activity and Intralipid clearance in very lowbirth-weight infants. J PEDIATR1981;98:617-22. 5. Ritthamel-Weinstein MR, Haugen K. Hypertriglyceridemia
4 60
6.
7.
8.
9.
Clinical and laboratory observations
The Journal of Pediatrics March 1989
in an infant with bronchopulmonary dysplasia. Nutr Clin Pract 1987;2:112-6. Greer FR, McCormick A, Kashyap ML, Glueck EJ. Late hypertriglyceridemia in very low birth weight infants fed human milk exclusively. J PEDIATR1987;111:466-9. Smigura FC, Bryan H, Angel A. Postheparin lipase activity in newborn infants. In: Hahn P, Segal S, Israels S, eds. The role of fat in intravenous feeding of the newborn. Dorval, Quebec; Pharmacia (Canada) Ltd., 1974:129. Rovamo L, Nikkila EA, Taskinen MR, Raivio K. Postheparin plasma lipopr0tein and hepatic lipases in preterm neonates. Pediatr Res 1984;18:1104-7. Lane DM, McConathy WJ. Factors affecting the lipid and apolipoprotein levels of cord sera. Pediatr Res 1983;17:8391.
10. Stahl GE, Spear ML, Hamosh M. Intravenous administration of lipid emulsions to premature infants. Clin Perinatol 1986;13:133-63. 11. Rovamo L, Taskinen MR, Kuusi T, et al. Postheparin plasma lipase activities and plasma lipoproteins in newborn infants. Pediatr Res 1984;18:642. 12. Pereira G, Fox WW, Stanley CA, et al. Decreased oxygenation and hyperlipemia during intravenous fat infusions in premature infants. Pediatrics 1980;66:26-30. 13. Levene MI, Wigglesworth JS, Desai R. Pulmonary fat accumulation after Intralipid infusion in the preterm infant. Lancet 1980;2:815-8. 14. Dahms BB, Halpin TC. Pulmonary arterial lipid deposit in newborn infants receiving intravenous lipid infusion. J PEDIATR 1980;97:800-5.
FELLOWSHIPS Available fellowships in pediatric subspecialties and those for general academic pediatric training are listed once a year, in May, in THE JOURNAL OF PEDIATRICS. Each October, forms for listing such fellowships are sent to the Chairman of the Department of Pediatrics at most major hospitals in the United States and Canada. Should you desire to list fellowships, a separate application must be made each year for each position. All applications must be returned to The C.V. Mosby Company by February 15 of the listing year to ensure publication. Additional forms will be supplied on request from the Journal Editing Department, The C.V. Mosby Company, 11830 Westline Industrial Drive, St. Louis, M O 63146-3318/314-872-8370.