Acla Predial,. Scand 68: 709-711, 1979
THE NUMBER OF POLYMORPHONUCLEAR LEUKOCYTES IN RELATION TO GESTATIONAL AGE IN THE NEWBORN L. COULOMBEL, M. DEHAN, G. TCHERNIA, C. HI LL and M. VIAL From the Laboratoire Celltral d' Hematologie and the Sen'ice de Reanil1lation Neonatale. Hopital AI/toine Bee/ere , Clamart. France
ABSTRACT. Coulombel, lo, Dehan, M., Tchernia, G., Hill , C. and Vial, M. (Laborstoire Central d'Hematologie and Service de rea nimation neonatale, Hopital Antoine Beclere, Clamart, France). The number of polymorphonuclear leukocytes in relation to gestational and post natal ages in non infected distressed newborns. Acta Paediatr Scand, 68: 709, ]979, -173 distressed newborn infants without evidence of bacterial infection were investigated at 12-hour intervals for the number of polymorphonuclear leukocytes during the first 5 days of life. The results showed a significant difference in the number of polymorphonuclear leukocytes in relation to both gestational and post natal ages. The study stresses the necessity of taking into account these differences in interpreting neutropenia as a sign of bacterial infection in neonates. KEY WORDS: Newborn infants, bacterial infection , neutropenia
Within the first days of life, the existe nce of ne utropeni a i usually considered a sign of se riou s bacterial infection ( I, 2, 5, 6). In an attempt to define numerical limits on the definition of neutrope nia , we studied, in a population of distressed but non infected newborns, the vari atio ns in the number of polymorphonuclear leukocytes (PMN) in relation both to gestational a nd post natal ages.
MATERIAL AND METHODS All newborn infants of age less than 5 day s admitted to the neonatal intensive care unit during a nine month period were included in this study . All these infants had some kind of distress a nd none of them cou ld be considered as normal infants. 70 % of all blood sa mples and 85 % of the fir t 48 hours sam ples were obtained by umbilical catheter. Other sa mples were obtained by heel pricks. The variation of hemoglobin values in the different sa mples drawn at 12 hour intervals did not exceed 15 gil. Thus, we assumed th at all wac counts cou ld be taken in account and compared, even when the sampling technique was different. Total leukocy te enumeration was performed by a Co ult er S blood cell counter and was verified by hemocytometer if the white blood cell cou nt was less than 3000/0101 3 • A differential 46 - 792875
count was pelformed by classifying 200 nucleated cells on a smear stained wit h May-Griinwald-Giemsa . These observations were initia ted when the infant entered the unit . were repeated every 12 hours up to 48 hours of age and were continued every 24 hours afterwards through the 4th day of life. 240 newborn infants were included in this inve tigation . 67 were excluded from th e tati tical analysis. either because bacterial infection was verified (15 infants) or becau e infection was thought probable but not proven by bacteriological results (52 infants) . The remai ning 173 infants without bacterial infection were retained for the tatistical analysis . They were subdivided into 3 groups of different gestational age . Namely group I : 37 weeks or more , group 2: 33 to 36 weeks and group 3: 32 week or less. Among these 173 newborns. sample during the first 12 hours of life were obtained for 132 infants . For the lime intervals after the first 12 hours . we included data from all available patients even if the early blood samples had not been obtained.
RESULTS A shown in Fig. J, wi thin the fir t twelve hours of life in 132 newborn , a correlation appeared between ge tational age and the number of PMN/mm 3 : as gestational age progressed the mean number of PMN/mm 3 progre sively increased. During this initial 12 hour period the mean ±2 S.E.M. number of Aclt/ Pa edi",/' 5u/IIcl6Ii
710
L. Coulombel ef 01 .
PMN / mm 3
20000
.
." " ". I " ,. ." ". . : " " -'. ., .;/ .' : , ..-. .
/
10000
.
".."
.
i
>< .
,"..
0/
.,. " o~
25
__
".
~
•
____
30
~
____
35
~
____-.
40 GA (weeks)
Fig . I . PMN/mm 3 in relation to gestational age in 132 newborns within the first 12 hours of life. The formula for the equation of the regression line allowing calculation of the number of PMN in relation to ge tational age is: PMN x GA-16700. r=O.52p li
capable of granulocyte differentiation in other environments as shown by Moore & Williams (3) . In vivo this granulocytic differentiation mainly occurs in bone marrow during the last gestational week and gradually increases. This process can explain the correlation between the number of PMN and the gestational age. The loss of this correlation during the first week after birth suggests that natal or postnatal events lead to a regulation of the granulocyte population which eliminate the differences in children of various gestational ages by the end of the I st week of life. This fact, to our knowledge , had not been found in previous studies. In ick newborn infants, early detection and prompt treatment of bacterial infection is necessary to avoid a fulminant course of disease leading frequently to death . Since neutropenia ha been shown to represent a useful and early ign of severe bacterial infections, it appears important to define the limits of this criterion. Our results emphasize the neces ity of referring to both gestational and postnatal ages in interpreting the significance of the number of PMN in sick newborns. For example (Fig. 2) , 5000 PMN/mm 3 at less than 12 hours of age is a normal figure for an infant born at 32 weeks of ge tation, but i pathologic for a term neonate of the same postnatal age. At present, these figures are employed routinely in our intensive care unit and are useful in the diagno i of neonatal infection. Gestation
Polymorphonuclear neutrophlls tX10'/ mm3 )
tweeks)
• < 32 . 32-37 • :>37
15
10
'..
5
Birth
12
24
..
l'
36
48
Fig. 2. Evolution of PMN/mm gestational groups.
.,
'.72
3
a
.L
96 Age thou's)
compared in the 3
Definition oJ nelltropenia in newborns
ACKNOWLEDGEMENTS This study has been granted by the Caisse Regionale d'Assurance Maladie de rile de France.
REFERENCES I. Gregory , 1. & Hey , E. : Blood neutrophil response to bacterial infection in the first month of life. Arch Dis Child, 47: 747, 1972. 2. Kuchler, H., Fricker, H . & Gugler, E .: La formule sanguine dan Ie diagnostic precoce de la septicemie du nouveau-ne . Helv Paediatr A cta , 31 : 33 , 1976. 3. Moore , M . A. S. & Williams, N .: Analysis of proliferation and differentiation of fetal granulocyte macrophage progenitor cells in haemopoietic tissue. Cell Tisslle Killet . 6: 461 , 1973.
711
4. Oski, F. A. & Naiman , J . L. : Hematologic problems il1 th e newborn . W . B. Saunders Company, Philadelphia 1972, 2nd ed. , p . 327 . 5. Xanthou, M. : Leucocyte blood picture in ill newborn babies. Arch Dis Child. 47: 741 , 1972. 6. Zipurski. A. & Jaber , H . M.: The haematology of bacterial infection in newborn infants . Clin Ha ematol, 7. 175, 1978. Submitted July 28, 1978 Accepted FebI'. 5, 1979 (G. T .) Laboratoire Central d'Hematologie H6pital Antoine Beclere 157, Rue de la Porte de Trivaux 92141 Clamart France
Acta Plledilllr S{,(IIIt! 6X
THE NUMBER OF POLYMORPHONUCLEAR LEUKOCYTES IN RELATION TO GESTATIONAL AGE IN THE NEWBORN L. COULOMBEL, M. DEHAN, G. TCHERNIA, C. HI LL and M. VIAL From the Laboratoire Celltral d' Hematologie and the Sen'ice de Reanil1lation Neonatale. Hopital AI/toine Bee/ere , Clamart. France
ABSTRACT. Coulombel, lo, Dehan, M., Tchernia, G., Hill , C. and Vial, M. (Laborstoire Central d'Hematologie and Service de rea nimation neonatale, Hopital Antoine Beclere, Clamart, France). The number of polymorphonuclear leukocytes in relation to gestational and post natal ages in non infected distressed newborns. Acta Paediatr Scand, 68: 709, ]979, -173 distressed newborn infants without evidence of bacterial infection were investigated at 12-hour intervals for the number of polymorphonuclear leukocytes during the first 5 days of life. The results showed a significant difference in the number of polymorphonuclear leukocytes in relation to both gestational and post natal ages. The study stresses the necessity of taking into account these differences in interpreting neutropenia as a sign of bacterial infection in neonates. KEY WORDS: Newborn infants, bacterial infection , neutropenia
Within the first days of life, the existe nce of ne utropeni a i usually considered a sign of se riou s bacterial infection ( I, 2, 5, 6). In an attempt to define numerical limits on the definition of neutrope nia , we studied, in a population of distressed but non infected newborns, the vari atio ns in the number of polymorphonuclear leukocytes (PMN) in relation both to gestational a nd post natal ages.
MATERIAL AND METHODS All newborn infants of age less than 5 day s admitted to the neonatal intensive care unit during a nine month period were included in this study . All these infants had some kind of distress a nd none of them cou ld be considered as normal infants. 70 % of all blood sa mples and 85 % of the fir t 48 hours sam ples were obtained by umbilical catheter. Other sa mples were obtained by heel pricks. The variation of hemoglobin values in the different sa mples drawn at 12 hour intervals did not exceed 15 gil. Thus, we assumed th at all wac counts cou ld be taken in account and compared, even when the sampling technique was different. Total leukocy te enumeration was performed by a Co ult er S blood cell counter and was verified by hemocytometer if the white blood cell cou nt was less than 3000/0101 3 • A differential 46 - 792875
count was pelformed by classifying 200 nucleated cells on a smear stained wit h May-Griinwald-Giemsa . These observations were initia ted when the infant entered the unit . were repeated every 12 hours up to 48 hours of age and were continued every 24 hours afterwards through the 4th day of life. 240 newborn infants were included in this inve tigation . 67 were excluded from th e tati tical analysis. either because bacterial infection was verified (15 infants) or becau e infection was thought probable but not proven by bacteriological results (52 infants) . The remai ning 173 infants without bacterial infection were retained for the tatistical analysis . They were subdivided into 3 groups of different gestational age . Namely group I : 37 weeks or more , group 2: 33 to 36 weeks and group 3: 32 week or less. Among these 173 newborns. sample during the first 12 hours of life were obtained for 132 infants . For the lime intervals after the first 12 hours . we included data from all available patients even if the early blood samples had not been obtained.
RESULTS A shown in Fig. J, wi thin the fir t twelve hours of life in 132 newborn , a correlation appeared between ge tational age and the number of PMN/mm 3 : as gestational age progressed the mean number of PMN/mm 3 progre sively increased. During this initial 12 hour period the mean ±2 S.E.M. number of Aclt/ Pa edi",/' 5u/IIcl6Ii
710
L. Coulombel ef 01 .
PMN / mm 3
20000
.
." " ". I " ,. ." ". . : " " -'. ., .;/ .' : , ..-. .
/
10000
.
".."
.
i
>< .
,"..
0/
.,. " o~
25
__
".
~
•
____
30
~
____
35
~
____-.
40 GA (weeks)
Fig . I . PMN/mm 3 in relation to gestational age in 132 newborns within the first 12 hours of life. The formula for the equation of the regression line allowing calculation of the number of PMN in relation to ge tational age is: PMN x GA-16700. r=O.52p li
capable of granulocyte differentiation in other environments as shown by Moore & Williams (3) . In vivo this granulocytic differentiation mainly occurs in bone marrow during the last gestational week and gradually increases. This process can explain the correlation between the number of PMN and the gestational age. The loss of this correlation during the first week after birth suggests that natal or postnatal events lead to a regulation of the granulocyte population which eliminate the differences in children of various gestational ages by the end of the I st week of life. This fact, to our knowledge , had not been found in previous studies. In ick newborn infants, early detection and prompt treatment of bacterial infection is necessary to avoid a fulminant course of disease leading frequently to death . Since neutropenia ha been shown to represent a useful and early ign of severe bacterial infections, it appears important to define the limits of this criterion. Our results emphasize the neces ity of referring to both gestational and postnatal ages in interpreting the significance of the number of PMN in sick newborns. For example (Fig. 2) , 5000 PMN/mm 3 at less than 12 hours of age is a normal figure for an infant born at 32 weeks of ge tation, but i pathologic for a term neonate of the same postnatal age. At present, these figures are employed routinely in our intensive care unit and are useful in the diagno i of neonatal infection. Gestation
Polymorphonuclear neutrophlls tX10'/ mm3 )
tweeks)
• < 32 . 32-37 • :>37
15
10
'..
5
Birth
12
24
..
l'
36
48
Fig. 2. Evolution of PMN/mm gestational groups.
.,
'.72
3
a
.L
96 Age thou's)
compared in the 3
Definition oJ nelltropenia in newborns
ACKNOWLEDGEMENTS This study has been granted by the Caisse Regionale d'Assurance Maladie de rile de France.
REFERENCES I. Gregory , 1. & Hey , E. : Blood neutrophil response to bacterial infection in the first month of life. Arch Dis Child, 47: 747, 1972. 2. Kuchler, H., Fricker, H . & Gugler, E .: La formule sanguine dan Ie diagnostic precoce de la septicemie du nouveau-ne . Helv Paediatr A cta , 31 : 33 , 1976. 3. Moore , M . A. S. & Williams, N .: Analysis of proliferation and differentiation of fetal granulocyte macrophage progenitor cells in haemopoietic tissue. Cell Tisslle Killet . 6: 461 , 1973.
711
4. Oski, F. A. & Naiman , J . L. : Hematologic problems il1 th e newborn . W . B. Saunders Company, Philadelphia 1972, 2nd ed. , p . 327 . 5. Xanthou, M. : Leucocyte blood picture in ill newborn babies. Arch Dis Child. 47: 741 , 1972. 6. Zipurski. A. & Jaber , H . M.: The haematology of bacterial infection in newborn infants . Clin Ha ematol, 7. 175, 1978. Submitted July 28, 1978 Accepted FebI'. 5, 1979 (G. T .) Laboratoire Central d'Hematologie H6pital Antoine Beclere 157, Rue de la Porte de Trivaux 92141 Clamart France
Acta Plledilllr S{,(IIIt! 6X
