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Neutrophil alkaline phosphatase levels in normal and abnormal pregnancy
Neutrophil alkaline phosphatase levels in normal and abnormal pregnancy M.
G.
ELDER,
F.
BONELLO,
J.
ELLUL
Guardamangia,
M.B., M.D.,
CH.B.,
F.R.C.S.E.,
M.R.C.O.G.
D.(OBST.)R.C.O.G.
Malta
Seven hundred and thirty-one neutrophil alkaline phosphatase (NAP) estimations were carried out during normal and abnormal pregnancies. The normal range of activity is defined, and it is shown that in pregnancies complicated by hypertension, dysmaturity, fetal distress, or perinatal death the NAP activity is lower than normal. Despite this, the value of the estimations in the prediction of these complications is minimal.
ALKALINE phosphatase activity has been shown to be raised with infection,l pregnancy,2p 3 and after the administration of adrenocorticotropic hormone* and estrone.5 It has been suggested697 that leukocyte alkaline phosphatase activity is lower than normal in cases of pre-eclamptic toxemia. The present study was undertaken to assess in more detail the role of NAP estimations as a test of placental function. This paper will evaluate the NAP results, while their relationship to 2 other tests will be the basis of a subsequent paper.
cated by hypertension, dysmaturity, fetal distress, and perinatal death. Hypertension was mild-blood pressure 140/90 to 150/100 mm. Hg-or moderate to severe-over 150/100 mm. Hg. Many patients had unclassifiable hypertension, and no attempt was made to differentiate these from cases of essential hypertension or pre-eclamptic toxemia. Dysmaturity was defined according to the criteria used by Elder and associates.s Fetal distress was defined as a fetal heart rate of less than 100 beats per minute, recorded on more than one occasion, or the presence of meconium in the liquor amnii. Cases of proved or suspected infection were excluded.
LEUKOCYTE
Material
and
methods
There were 731 NAP estimations carried out on 226 women during pregnancy, The distribution of these is shown in Table I. Smears from the buffy coat were fixed and stained according to the method described by Climie and associates,s and 100 consecutive neutrophils were scored with the use of their criteria. Statistical comparison of groups was carried out by the Mann-Whitney test. The groups studied were those with normal pregnancies and pregnancies compliFrom the Department Gynaecology, Royal
Results
Table II shows the results of NAP estimations obtained during normal pregnancy; Tables III and IV, during hypertensive pregnancies; and Table V, during pregnancies complicated by fetal distress. Forty-eight NAP scores were obtained from 18 patients whose pregnancies were complicated by dysmaturity but not by hypertension. The mean value is 113.2 _+ 18.6. Fifteen NAP scores were obtained from 7 cases with perinatal deaths, the mean value being 92.9 + 21.2.
of Obstetrics and University of Malta.
663
Table I. The distribution of NAP estimations carried out during normal and abnormal pregnancies No.
of
patients
Normal pregnancy Mild hypertension Moderate to severe hypertension Dysmaturity uncomplicated by hypertension Fetal distress* Perinatal loss* Totals “Figures in parentheses other categories.
No. 336 160
51
169
:9 (5) 7 (1) 226 are the numben
Comment
/
5 S.D.
117.8 136.1 121.0
29.7 19.3 12.9
i: 33 34 35 36 37 38 39 40 41 42
20 23 22 34 30 39 37 36 28 19 9 10
124.0 127.3 126.9 127.9 l”1.8 lS3.3 1’0.0 11’4.6 195.3 I i8.i ll”.? 106.k
10.9 12.0 15.3 13.2 15.7 19.5 18.4 18.6
in
All the complications of pregnancy studied were associated with NAP scores significantly lower than normal. This may be
I
Mean
5 13 11
731
There is no correlation between the week of gestation and the NAP score, except in cases of moderate to severe hypertension (r = -0.46, p < 0.001) and perinatal death (r = -0.824, p < 0.001). All groups had NAP values significantly lower than normal, these being dysmaturity (p < 0.03), fetal distress (p < O.OOOl), mild hypertension (p < lo-‘), and moderate to severe hypertension (p < lo-*). The normal range is taken as 2 standard deviations from the mean, and 5 patients each had one score below this range. Twenty-nine patients had NAP estimations between 1 and 5 weeks prior to the onset of hypertension. Fourteen (48 per cent) of these had scores outside the normal range, this difference from the normal group being significant (p < 0.001) . Four of the 7 cases of perinatal death had scores outside the normal range, and this number is also significantly different from the normal group (p < 0.001). The number of cases of fetal distress and dysmaturity were not significantly different, being 3 (p > 0.3) and 2 (p > 0.2)) respectively. No correlation exists between fetal weight and the mean NAP score between 30 weeks and delivery (r = 0.03).
of
estimations
10-19 20-29 30
48 70 (17) 15 (1) not included
No.
Weeks of gestation
of
estimations
103 48
Table II. N.4P estimations in normal pregnancy . . --.-.-__- _ - .-.---..-... _ .- ..-
22.3 17.9 26.0 18.9 -
Table III. NAP estimations in pregnancies complicated by mild hypertension Weeks of gestation
30 31 32 33 34 35 36 37 38 39 40 41 42
No. of estimations
-
8 8 10 10 13 18 21 25 22 11 6 6 2
Mean
109.5 113.1 120.0 120.7 108.9 111.5 115.9 113.2 112.5 104.5 108.5 95.0 - 105.0
-I S.D.
14.0 13.3 19.4 25.8 19.3 19.2 18.8 20.0 16.9 18.9 14.8 16.4 0
due to the abnormal production or metabolism of placental steroids, perhaps estrogenSlo Caution should be exercised in the interpretation of these results, for, although statistically different groups have been identified, the great overlap of scores considerably reduces the value that can be placed on an individual result. In cases of fetal distress and dysmaturity, the almost complete overlap of NAP scores into the normal range and, in the latter group, the absence of correlation with fetal weight make the test valueless for prediction.
This study confirms that NAP scores are lower in hypertensive pregnancies and that the drop may occur some weeks prior to the
Volume Number
111 5
NAP levels in pregnancy
Table IV. NAP estimations in pregnancies complicated by moderate to severe hypertension Weeks gestation
of
No. of estimations
30 31 32 33 34 35 36 37 38 39 40 41 42
5 6 15 16 15 21 28 30 17 9 4 2 1
Table V. NAP estimations in pregnancies complicated by fetal distress Weeks of eestation
Mean
+ S.D.
30
95.6 101.5 96.1 101.1 110.6 100.5 101.5 98.2 104.1 98.1 82.5 84.0 53.0
9.3 16.5 14.3 13.2 22.1 11.2 15.9 15.5 30.6 15.2 17.1 25.4 -
ii”: 33 34 35 36 37 38 39 40 41 42
onset of hypertension, 6y7 but there is a much greater overlap of values with the normal than was found by Sadovsky and co-workers.O This is such as to make the prognostic value of the test, in these cases, minimal, despite a significant number of women having abnormal scores before the onset of their hypertension.
2. 3.
4.
5. 6.
Valentine, W. N., and Beck, W. S.: J. Lab. Clin. Med. 38: 39, 1951. Pritchard, J. A.: J. Lab. Clin. Med. 50: 432, 1957. Polishuk, W. Z., Diamnnt, Y. Z., Zuckerman, H., and Sadovsky, E.: AM. J. OBSTET. GYNECOL. 107: 604, 1970. Valentine, W. N., Follette, J. H., Hardin, E. B., Beck, W. S., and Lawrence, J. S.: J. Lab. Clin. Med. 44: 219, 1954. Polishuk, W. Z., Zuckerman, H., and Diamant, Y.: Fertil. Steril. 19: 901, 1968. Sadovsky, E., Diamant, Y. Z., Zuckerman,
No. of estimations 4 5 4 5 6 8 9 8 5 6 7 2 1
Mean
k S.D.
112.5 111.4 108.5 116.4 109.0 104.8 121.3 112.9 115.8 111.7 113.6 108.5 106.0
23.7 18.9 15.4 13.5 11.2 11.1 18.4 20.1 26.1 11.5 23.4 36.1
In cases with perinatal deaths, there is a marked fall in values as pregnancy proceeds, and a significant number of women had abnormal scores. However, as nearly half of the estimations fell within the normal range the test is unlikely to be of prognostic significance. A larger number of such cases should be studied before reaching a firm conclusion.
REFERENCES
1.
665
7.
8.
9.
10.
H., and Polishuk, W. Z.: J. Obstet. Gynaecol. Br. Commonw. 76: 538, 1969. Zuckerman, H., Sadovsky, E., Diamant, Y. Z., and Polishuk, W. Z.: Isr. J. Med. Sci. 5: 1159, 1969. Climie, A. R. W., Heinrichs, W. L., and Foster, I. J.: Am. J. Clin. Pathol. 38: 95, 1962. Elder, M. G., Burton, E. R., Gordon, H., Hawkins, D. F., and McClure, Browne, J. Cl.: J. Obstet. Gynaecol. Br. Commonw. 77: 481, 1970. Elder, M. G., Bonello, F., and Ellul, J.: AM. J. OBSTET. GYNECOL. 111: 319, 1971.
G.
ELDER,
F.
BONELLO,
J.
ELLUL
Guardamangia,
M.B., M.D.,
CH.B.,
F.R.C.S.E.,
M.R.C.O.G.
D.(OBST.)R.C.O.G.
Malta
Seven hundred and thirty-one neutrophil alkaline phosphatase (NAP) estimations were carried out during normal and abnormal pregnancies. The normal range of activity is defined, and it is shown that in pregnancies complicated by hypertension, dysmaturity, fetal distress, or perinatal death the NAP activity is lower than normal. Despite this, the value of the estimations in the prediction of these complications is minimal.
ALKALINE phosphatase activity has been shown to be raised with infection,l pregnancy,2p 3 and after the administration of adrenocorticotropic hormone* and estrone.5 It has been suggested697 that leukocyte alkaline phosphatase activity is lower than normal in cases of pre-eclamptic toxemia. The present study was undertaken to assess in more detail the role of NAP estimations as a test of placental function. This paper will evaluate the NAP results, while their relationship to 2 other tests will be the basis of a subsequent paper.
cated by hypertension, dysmaturity, fetal distress, and perinatal death. Hypertension was mild-blood pressure 140/90 to 150/100 mm. Hg-or moderate to severe-over 150/100 mm. Hg. Many patients had unclassifiable hypertension, and no attempt was made to differentiate these from cases of essential hypertension or pre-eclamptic toxemia. Dysmaturity was defined according to the criteria used by Elder and associates.s Fetal distress was defined as a fetal heart rate of less than 100 beats per minute, recorded on more than one occasion, or the presence of meconium in the liquor amnii. Cases of proved or suspected infection were excluded.
LEUKOCYTE
Material
and
methods
There were 731 NAP estimations carried out on 226 women during pregnancy, The distribution of these is shown in Table I. Smears from the buffy coat were fixed and stained according to the method described by Climie and associates,s and 100 consecutive neutrophils were scored with the use of their criteria. Statistical comparison of groups was carried out by the Mann-Whitney test. The groups studied were those with normal pregnancies and pregnancies compliFrom the Department Gynaecology, Royal
Results
Table II shows the results of NAP estimations obtained during normal pregnancy; Tables III and IV, during hypertensive pregnancies; and Table V, during pregnancies complicated by fetal distress. Forty-eight NAP scores were obtained from 18 patients whose pregnancies were complicated by dysmaturity but not by hypertension. The mean value is 113.2 _+ 18.6. Fifteen NAP scores were obtained from 7 cases with perinatal deaths, the mean value being 92.9 + 21.2.
of Obstetrics and University of Malta.
663
Table I. The distribution of NAP estimations carried out during normal and abnormal pregnancies No.
of
patients
Normal pregnancy Mild hypertension Moderate to severe hypertension Dysmaturity uncomplicated by hypertension Fetal distress* Perinatal loss* Totals “Figures in parentheses other categories.
No. 336 160
51
169
:9 (5) 7 (1) 226 are the numben
Comment
/
5 S.D.
117.8 136.1 121.0
29.7 19.3 12.9
i: 33 34 35 36 37 38 39 40 41 42
20 23 22 34 30 39 37 36 28 19 9 10
124.0 127.3 126.9 127.9 l”1.8 lS3.3 1’0.0 11’4.6 195.3 I i8.i ll”.? 106.k
10.9 12.0 15.3 13.2 15.7 19.5 18.4 18.6
in
All the complications of pregnancy studied were associated with NAP scores significantly lower than normal. This may be
I
Mean
5 13 11
731
There is no correlation between the week of gestation and the NAP score, except in cases of moderate to severe hypertension (r = -0.46, p < 0.001) and perinatal death (r = -0.824, p < 0.001). All groups had NAP values significantly lower than normal, these being dysmaturity (p < 0.03), fetal distress (p < O.OOOl), mild hypertension (p < lo-‘), and moderate to severe hypertension (p < lo-*). The normal range is taken as 2 standard deviations from the mean, and 5 patients each had one score below this range. Twenty-nine patients had NAP estimations between 1 and 5 weeks prior to the onset of hypertension. Fourteen (48 per cent) of these had scores outside the normal range, this difference from the normal group being significant (p < 0.001) . Four of the 7 cases of perinatal death had scores outside the normal range, and this number is also significantly different from the normal group (p < 0.001). The number of cases of fetal distress and dysmaturity were not significantly different, being 3 (p > 0.3) and 2 (p > 0.2)) respectively. No correlation exists between fetal weight and the mean NAP score between 30 weeks and delivery (r = 0.03).
of
estimations
10-19 20-29 30
48 70 (17) 15 (1) not included
No.
Weeks of gestation
of
estimations
103 48
Table II. N.4P estimations in normal pregnancy . . --.-.-__- _ - .-.---..-... _ .- ..-
22.3 17.9 26.0 18.9 -
Table III. NAP estimations in pregnancies complicated by mild hypertension Weeks of gestation
30 31 32 33 34 35 36 37 38 39 40 41 42
No. of estimations
-
8 8 10 10 13 18 21 25 22 11 6 6 2
Mean
109.5 113.1 120.0 120.7 108.9 111.5 115.9 113.2 112.5 104.5 108.5 95.0 - 105.0
-I S.D.
14.0 13.3 19.4 25.8 19.3 19.2 18.8 20.0 16.9 18.9 14.8 16.4 0
due to the abnormal production or metabolism of placental steroids, perhaps estrogenSlo Caution should be exercised in the interpretation of these results, for, although statistically different groups have been identified, the great overlap of scores considerably reduces the value that can be placed on an individual result. In cases of fetal distress and dysmaturity, the almost complete overlap of NAP scores into the normal range and, in the latter group, the absence of correlation with fetal weight make the test valueless for prediction.
This study confirms that NAP scores are lower in hypertensive pregnancies and that the drop may occur some weeks prior to the
Volume Number
111 5
NAP levels in pregnancy
Table IV. NAP estimations in pregnancies complicated by moderate to severe hypertension Weeks gestation
of
No. of estimations
30 31 32 33 34 35 36 37 38 39 40 41 42
5 6 15 16 15 21 28 30 17 9 4 2 1
Table V. NAP estimations in pregnancies complicated by fetal distress Weeks of eestation
Mean
+ S.D.
30
95.6 101.5 96.1 101.1 110.6 100.5 101.5 98.2 104.1 98.1 82.5 84.0 53.0
9.3 16.5 14.3 13.2 22.1 11.2 15.9 15.5 30.6 15.2 17.1 25.4 -
ii”: 33 34 35 36 37 38 39 40 41 42
onset of hypertension, 6y7 but there is a much greater overlap of values with the normal than was found by Sadovsky and co-workers.O This is such as to make the prognostic value of the test, in these cases, minimal, despite a significant number of women having abnormal scores before the onset of their hypertension.
2. 3.
4.
5. 6.
Valentine, W. N., and Beck, W. S.: J. Lab. Clin. Med. 38: 39, 1951. Pritchard, J. A.: J. Lab. Clin. Med. 50: 432, 1957. Polishuk, W. Z., Diamnnt, Y. Z., Zuckerman, H., and Sadovsky, E.: AM. J. OBSTET. GYNECOL. 107: 604, 1970. Valentine, W. N., Follette, J. H., Hardin, E. B., Beck, W. S., and Lawrence, J. S.: J. Lab. Clin. Med. 44: 219, 1954. Polishuk, W. Z., Zuckerman, H., and Diamant, Y.: Fertil. Steril. 19: 901, 1968. Sadovsky, E., Diamant, Y. Z., Zuckerman,
No. of estimations 4 5 4 5 6 8 9 8 5 6 7 2 1
Mean
k S.D.
112.5 111.4 108.5 116.4 109.0 104.8 121.3 112.9 115.8 111.7 113.6 108.5 106.0
23.7 18.9 15.4 13.5 11.2 11.1 18.4 20.1 26.1 11.5 23.4 36.1
In cases with perinatal deaths, there is a marked fall in values as pregnancy proceeds, and a significant number of women had abnormal scores. However, as nearly half of the estimations fell within the normal range the test is unlikely to be of prognostic significance. A larger number of such cases should be studied before reaching a firm conclusion.
REFERENCES
1.
665
7.
8.
9.
10.
H., and Polishuk, W. Z.: J. Obstet. Gynaecol. Br. Commonw. 76: 538, 1969. Zuckerman, H., Sadovsky, E., Diamant, Y. Z., and Polishuk, W. Z.: Isr. J. Med. Sci. 5: 1159, 1969. Climie, A. R. W., Heinrichs, W. L., and Foster, I. J.: Am. J. Clin. Pathol. 38: 95, 1962. Elder, M. G., Burton, E. R., Gordon, H., Hawkins, D. F., and McClure, Browne, J. Cl.: J. Obstet. Gynaecol. Br. Commonw. 77: 481, 1970. Elder, M. G., Bonello, F., and Ellul, J.: AM. J. OBSTET. GYNECOL. 111: 319, 1971.