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Journal of the American College of Nutrition, Vol. 26, No. 5, 412-415 (2007)
Published by the American College of Nutrition

Increased Energy Expenditure after Dilutional Exchange Transfusion for Neonatal Polycythemia

Shaul Dollberg, MD, FACN, Ronela Marom, MD, Francis B. Mimouni, MD, FACN and Yoav Littner, MD

Departments of Neonatology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center (S.D., R.M., F.B.M., Y.L.)
Sackler Faculty of Medicine, Tel Aviv University (S.D., F.B.M., Y.L.), Tel Aviv, ISRAEL

Address correspondence to: Shaul Dollberg, MD, Department of Neonatology, Lis Maternity Hospital, Tel Aviv-Sourasky Medical Center, 6 Weizman Street, Tel Aviv, 64239, ISRAEL. E-mail: dolberg{at}post.tau.ac.il


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 REFERENCES
 
Objective: Hypothermia is a known symptom of neonatal polycythemia (NP) and its pathophysiology is unclear. The effect of partial dilutional exchange transfusion (PET) upon resting energy expenditure (REE) is unknown. We aimed to test the hypothesis that PET leads to an increase in REE.

Study Design: 11 patients with NP who underwent PET and 10 controls without polycythemia were studied. NP was defined as a venous HCT ≥0.65. Per protocol, symptomatic infants and/or those with venous HCT ≥0.70 underwent PET. REE was measured just prior and 23 hours after PET in patients with NP and at identical ages in the control group. Infants were studied in a skin servo controlled radiant warmer, while clinically and thermally stable, prone and asleep. Measurements were stopped during body movements (less than 5% of the time of measurement). Metabolic measurements were performed by indirect calorimetry, using the Deltatrac II Metabolic monitor (Datex-Ohmeda, Helsinki, Finland). This instrument uses the principle of the open circuit system that allows continuous measurements of oxygen consumption (VO2) and carbon dioxide production (VCO2) using a constant flow generator. REE measurements were corrected for the infant weight (Kcal/kg/d). Comparison of REE values between groups was performed using paired Wilcoxon ranked test.

Results: Patients with and without NP had nearly identical baseline REE. In patients with NP, REE increased from 44.0 ± 6.6 Kcal/Kg/d to 48.3 ± 5.1 Kcal/Kg/d after PET (P<0.05). Furthermore, the increase in REE following PET correlated inversely with the decrease in hematocrit. There was no significant change in REE over time in the control group. In the NP group, symptomatic infants (n=5) had a significantly greater increase in REE following PET than non-symptomatic ones (1.4 ± 6.3 vs. 7.8 ± 4.9 Kcal/Kg/d, p<0.05).

Conclusions: Energy expenditure of polycythemic infants increases following PET, in a manner proportional to the decrease in hematocrit. Symptomatic polycythemic infants have a greater rise in REE following PET than non-symptomatic ones. We speculate that polycythemia leads to a decreased REE that might be remedied by PET.

Key words: polycythemia, hyperviscosity, exchange transfusion, energy expenditure, metabolic rate


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 REFERENCES
 
Neonatal polycythemia (NP), generally defined as a venous hematocrit >0.65 [1], is frequently diagnosed after birth, in particular if a routine screening program is established at the time the neonatal hematocrit is the highest, i.e. at 2 to 4 hours of age [1,2]. Most infants are asymptomatic, since polycythemia is rarely diagnosed in institutions where routine screening is not performed [3]. Hypothermia has been associated with polycythemia [4] the mechanism of which is unknown. The purpose of our study was to measure resting energy expenditure (REE) in polycythemic infants, and to determine the effect of partial dilutional exchange transfusion (PET) upon REE. As there is an increase in cardiac output and blood flow velocity following partial dilutional exchange transfusion (PET) [5] we tested the hypothesis that PET also leads to an increase in REE.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 REFERENCES
 
Patients
We recruited 11 consecutive patients with NP who underwent PET and 10 controls. In our institution, there is a routine screening program for NP. According to our protocol, at approximately 6 hours of life a heel stick complete blood count is obtained from every infant and a venous sample for spun hematocrit is obtained whenever the heel stick hematocrit exceeds 0.70. Neonatal polycythemia is then defined whenever the venous HCT exceeds 0.65. Each infant recognized as having NP is carefully examined and observed for potential symptoms of polycythemia and screened as well for hypoglycemia (whole blood glucose < 45 mg/dl). Per protocol (and as recommended by standard textbooks [6]), symptomatic infants and/or those with venous HCT ≥0.70 undergo PET. In practice, the PET is preformed at approximately 10–12 hours of age, using normal saline (0.9 g/100ml). In addition, a group of 10 healthy infants born after normal pregnancy, labor and delivery, were consecutively recruited in order to serve as a reference ("control group") for energy expenditure at this early age. The study was approved by our local Institutional Review Board and written informed consent was obtained from one of the parents.

Energy Expenditure Measurements
Resting energy expenditure was measured just prior and 23 ± 4.9 hours after PET. Infants without polycythemia who served as controls were measured at similar ages (approximately 11 hours of age and 23 ± 1.3 hours later). Measurements were obtained over a 20 minute period upon fully dressed infants, in an open-air bassinet. Because energy expenditure varies in infants throughout the day [7], and in particular in relation to feeding [8], we elected to observe patients for a period of 0.5 hour, while clinically and thermally stable (stable continuous skin temperature measurement between 36.0–36.5°C), prone and asleep and at least 2 hours after the last feeding. In order to further decrease the variability of the measurement, we stopped recording during body movements (less than 5% of the time of measurement). The PET was performed in all infants while they were placed in a skin servo controlled radiant warmer, set up to a skin temperature of 36 °C. Metabolic measurements were performed by indirect calorimetry, using the Deltatrac II Metabolic monitor (Datex-Ohmeda, Helsinki, Finland). This instrument uses the principle of the open circuit system that allows continuous measurements of oxygen consumption (VO2) and carbon dioxide production (VCO2) using a constant flow generator. The measurement ranges for both O2 consumption and CO2 production of 5–2000 ml/minute allow measurements in preterm infants with small tidal volumes. Prior to the measurement, the device performs a self-calibration based on independently measured barometric pressure. Additionally, periodic testing for accuracy was performed by alcohol burning according to the manufacturer instructions. This method is safe and allows prolonged measurements while allowing reasonable access to the infant for routine care. In our hands, the instrument has an intra-assay coefficient of variation of 3% [9].

Statistical Analyses
Energy expenditure measurements were expressed as such, and corrected for the infant weight (Kcal/kg/d). Comparison of REE values before and after PET or between measurements in the control group were performed using paired Wilcoxon ranked test. Comparison of REE values between symptomatic and asymptomatic infants was performed using Kruskal-Wallis test. Linear regression was used to study the correlation between the change in HCT before and after PET and the change in REE.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
REFERENCES
 
Basic demographic and clinical data are depicted in the Table 1. The study group was composed of infants without risk factors for polycythemia, except one infant who was small for gestational age born to a preeclamptic mother, and another one who was large for gestational age. There were no infants of diabetic mothers in this study group. Baseline REE was similar in both groups (Table 1). REE increased after PET in the NP group from 44.0 ± 6.6 Kcal/Kg weight/d to 48.3 ± 5.1 Kcal/Kg weight/d (0<0.05), while there was no significant change in REE in the control group over a similar period of time (Table 1). Symptomatic infants (n=5: hypoglycemia in 3 infants, grunting in one and a cyanotic spell in the fifth one) had a significantly greater increase in REE following PET than non-symptomatic ones (n= 6) (1.4 ± 6.3 vs. 7.8 ± 4.9 Kcal/Kg/d, p<0.05). Notably, all infants with hypoglycemia had a whole blood glucose >50 mg/dl at the time they underwent the metabolic measurement. The increase in REE following PET correlated inversely with the decrease in hematocrit (R2=51%, P=0.013) (Fig. 1).


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  		Table 1. Demographic and Laboratory Data of the Study Infants

 

Figure 1
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  		Fig. 1. The increase in energy expenditure following partial dilutional exchange transfusion (PET) significantly correlated inversely with the decrease in hematocrit during the exchange transfusion.

 

   DISCUSSION
 
We have demonstrated that in polycythemic infants, there is an increase of approximately 10% in REE after PET. This increase was observed after a period of approximately 1 day following the PET, and was not observed in control infants suited at the same post-natal ages. Moreover, in infants with NP, the degree of increase in REE after PET correlated with the degree of decrease in hematocrit and symptomatic infants had a significantly greater increase in REE following PET than non-symptomatic ones.

The current data may be understood in the following manner: the fact that REE increased following PET in polycythemic neonates may indicate that either polycythemia reduces REE, a phenomenon relieved by PET, or the procedure itself, rather than polycythemia, leads to an increase in REE. The first option is not likely, since, if polycythemia had reduced REE, we would have expected to see a higher REE in control infants at 11 hours, and a similar REE at 23 hours, which did not happen. Thus it is more probable that the increase in REE following PET was secondary to the procedure. In such case, it is theoretically possible that infants with NP, who were placed under radiant warmer during the procedure, may have increased their REE as a consequence of overheating. We do not believe this possibility to be true, since 1) Infants were not overheated, and their skin temperature was servo-controlled at a set up temperature of 36 °C over the whole period (approximately 1/2 hour) of the PET; 2) the effect of overheating, if any, was not likely to still be present 23 hours after the procedure, and 3) the increase in REE following PET occurred in a manner proportional to the decrease in hematocrit. Thus it is more likely that the increase in REE was related to the decrease in hematocrit per se. We can only speculate upon the mechanism of this increase. It is possible that the increase in cardiac output and the blood flow velocity in the carotid artery and the celiac artery described to occur after PET by Mandelbaum et al [5] may contribute to the observed increase in REE. Similar, but not identical findings were reported by Swetnam et al, who found a 32% increase in cardiac index, and a 80% increase in cutaneous blood flow following PET [10]. Similarly, Murphy et al showed an increase in left ventricular emptying rate following PET in asymptomatic infants with polycythemia [11]. For ethical reasons, we did not study a group of polycythemic infants with a Sham procedure, which would have enabled us to better understand the mechanism of the increase in REE following PET.

Symptomatic polycythemic infants had a greater rise in REE following PET than non-symptomatic ones. Three infants in the "symptomatic group" were hypoglycemic, although hypoglycemia had been corrected by the time they underwent the procedure. There is ample evidence that infants may utilize other substrates such as protein and fats to provide energy to the organs of the body, including the brain [12,13], which may in some fashion, affect oxygen consumption. Thus it is possible that the greater rise in REE following PET in infants who had experienced hypoglycemia may have been related to a different utilization of metabolic substrates.

In our study, it was not possible to correlate changes in REE with changes in body temperature, since, by design, all infants had the PET performed while they were kept in a skin servo controlled radiant warmer, and because REE was studied again 23 hours after the PET; at that time, they were clinically and thermally stable, prone and asleep. Thus, our study does not allow us to better understand the hypothermic tendency of some infants with polycythemia.

In summary, we found that REE of polycythemic infants increases following PET, in a manner proportional to the decrease in hematocrit. Symptomatic polycythemic infants have a greater rise in REE following PET than non-symptomatic ones. We speculate that PET leads to measurable changes in energy metabolism of the polycythemic neonate.

Received April 22, 2005. Accepted November 7, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 REFERENCES
 

  1. Shohat M, Reisner SH, Mimouni F, Merlob P: Neonatal polycythemia: II. Definition related to time of sampling.Pediatrics73 :11 –13,1984 .[Abstract/Free Full Text]
  2. Ramamurthy RS, Berlanga M: Postnatal alteration in hematocrit and viscosity in normal and polycythemic infants.J Pediatr110 :929 –934,1987 .[Medline]
  3. Wirth FH, Goldberg KE, Lubchenco LO: Neonatal hyperviscosity: I.Incidence. Pediatrics63 :833 –836,1979 .
  4. Larcan A, Stoltz JF, Gaillard S: Blood viscosity. Measurement and applications (hyper-and hypoviscosity syndromes).Nouv Presse Med18 :1411 –1415,1981 .
  5. Mandelbaum VH, Guajardo CD, Nelle M, Linderdamp O: Effects of polycythaemia and haemodilution on circulation in neonates.Arch Dis Child Fetal Neonatal Ed71 :F53 –F54,1994 .[Abstract/Free Full Text]
  6. Luchtman-Jones L, Schwartz AL, Wilson DB: The blood and hematopoietic system. In Fanaroff AA, Martin RJ (eds):"Neonatal Perinatal Medicine," 7th ed. St. Louis: Mosby, pp1204 –1205,2002 .
  7. Schulze K, Stefanski M, Masterson J, Kashyap S, Sanocka U, Forsyth M, Ramakrishnan R, Dell R: An analysis of the variability in estimates of bioenergetic variables in preterm infants.Pediatr Res20 :422 –427,1986 .[Medline]
  8. Lubetzky R, Vaisman N, Mimouni FB, Dollberg S: Energy expenditure in human milk versus formula fed preterm infants.J Pediatr143 :750 –753,2003 .[Medline]
  9. Dollberg S, Mimouni FB, Weintraub V: Energy expenditure in infants weaned from a convective incubator.Am J Perinatol21 :253 –256,2004 .[Medline]
  10. Swetnam SM, Yabek SM, Alverson DC: Hemodynamic consequences of neonatal polycythemia.J Pediatr110 :443 –447,1987 .[Medline]
  11. Murphy DJ, Reller MD, Meyer RA, Kaplan S: Left ventricular function in normal newborn infants and asymptomatic infants with neonatal polycythemia.Am Heart J112 :542 –547,1986 .[Medline]
  12. Adam PA, Raiha N, Rahiala EL, Kekomaki M: Oxidation of glucose and D-B-OH-butyrate by the early human neonatal brain.Acta Paediatr Scand64 :17 ,1975 .[Medline]
  13. Settergren G, Lindblad BS, Persson B: Cerebral blood flow and exchange of oxygen, glucose, ketone bodies, lactate, pyruvate and amino acids in anesthetized children.Acta Paediatr Scand69 :457 –465,1980 .[Medline]




This Article
Right arrow Abstract Freely available
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Right arrow Articles by Dollberg, S.
Right arrow Articles by Littner, Y.
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Right arrow Articles by Dollberg, S.
Right arrow Articles by Littner, Y.

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