Serum amylase changes during pregnancy RUDOLPH J.
KAISER,
EDWARD
LOUIS With
M.D.
BERK,
M.D.
FRIDHANDLER, the technical
PH.D.
assistance
KATHERINE
of
MONTGOMERY,
DEBORAH
WONG,
B.A
B.A.
Irvine, California Study
of the behavior of serum amylase activity in 200 pregnant women in various stages indicated that: (1) serum amylase rises gradually during pregnancy until the twenty-fifth week and thereafter falls slightly; (2) serum amylase values may be found in normal pregnant women during the second and third trimesters that exceed those in normal men and nonpregnant women; (3) during the second trimester of pregnancy there may be an alteration in the relative distribution of the pancreatic and salivary-type isoamylases with the salivary type tending to dominate. Knowledge of these changes is of importance in the clinical assessment of serum amylase values in pregnant women complaining of abdominal pain and other symptoms suggestive of complicating acute pancreatitis. An explanation for the observed changes is not readily available and further study is required. of pregnancy
Material
T H E L E V E L of serum amylase during pregnancy in human beings and in other animals has been reported differently by different observers.r+ Since some pregnant women develop abdominal pain and other symptoms that are clinically consistent with those associated with acute pancreatitis,6 it is of importance to know whether the serum amylase level found in such patients exceeds or is within the normal range. The study that forms the basis of this report was undertaken to help provide this information. From the Division of Gnstroenterology, Department of Medicine, University Irvine, Supported Foundation, Received Revised Accepted
by a grant Inc.
from
October
The John
California
A. Hartford Methods
for publication September
of
A total of 200 pregnant women attending the Prenatal Clinic of the Orange County Medical Center were selected for the purposes of this study. All of them were asymptomatic. None of them used any drugs other than prescribed vitamins, consumed alcohol more than occasionally or socially, smoked many cigarettes, or had a history of previous hepatic, gallstone, or pancreatic disease. Their ages ranged from 14 to 37 years. The group was comprised of white and black native Americans, as well as Americans of Mexican origin. Of the 200 women, 62 were in the first trimester of pregnancy, 78 were in the second trimester, and 60 were in the third trimester.
July
23, 1974.
A blood sample taken from each of the 200 subjects was examined for total serum amylase activity with an automated saccharogenic method.7 The reducing power generated is the measure of amylase activity and is expressed as milligrams of glucose per 100 ml. Certain samples obtained from subjects
12, 1974. 8, 1974.
Reprint requests: 1. Edward Berk, M.D., Department of Medicine, University of California, College of Medicine, Irvine, California 92664. 283
- _.,,.
Am. J. Obst .I
. 0
r’
140 -
8 -
130-
=
2 + :I S.E
..
IZO110 100 -
da ii 8 ? g
00 9070-
z
60 -
5 F ::
5040 -
z I
5
N=28
3020-
101 ,
N’42
N=24
N=28
N=25
N=28
N’24
,
,
,
,
,
21-25
26-X)
31-35
36-40
,
6-10
II-15
16-20
DURATION
OF PREGNANCY
(WEEKS)
Fig. 1. Mean ? 2 S.E. values for serum amylase during pregnancy. (N refers to number of patients in each 5 week period.)
Table I. Serum
amylase
6-10 11-15 16-20 21-25 26-30 31-35 36-40
during
activity studied
pregnancy
I
I
Serum amylase values (mg. of gIuAxe/lOO ml.)
I
I
I
I Weeksof pregnancy
values
I
I
28 42 24 28 25 28 25
27 24 52 54 58 57 52
I > 100
I
/N.-“lL~~-“‘..:-(,,..~ patients
S.E. 68 100 117 209 208 136 154
46 63 84 117 106 92 84
,
1.8 2.3 3.5 6.7 8.0 3.7 3.9
i$io 0 0 6 18 10 9 3
0 0 25 64 40 32 13
200
in each of the trimesters of pregnancy were selected for isoamylase analysis. The samples selected for this analysis were those showing high or low values of amylase activity as compared to the rest of the group in the respective trimester. Two of the samples examined were from patients in the first trimester of pregnancy, three were from patients in the second trimester, and three were from patients in the third trimester. The isoamylase pattern in each of these samples was determined by means of a chromatographic technique previously reported from this laboratory.*
~-.--,
:.,,I, I / 1
Results The serum amylase results of an earlier stud) made by us8 in a small group of 30 subject\ c’omposed of apparently normal men and nonpregnant women were recalculated. To help insure a normal distribution, each value was converted intc; its logarithm and the mean and standard deviation of these logarithms were calculated. The results indicated that a serum activity of 100 mg. of glucose per 100 ml. might better be considered the upper limit of normal rather than the level of 90 mg. of glucose per 100 ml. previously suggested.” By contrast with this value, the amylase value (mean + SE.), computed for each of the trimesters, rose from 52 rt 1.6 in the 62 patients in the first trimester, to 103 ? 4.0 in the 78 patients in the second trimester, and then diminished to 100 + 12.2 in the 60 patients in the third trimester. Corollary to this change in mean values was the fact that none of the 62 patients in the first trimester, 33 (42 per cent) of the 78 in the second trimester, and 13 (22 per cent) of the 60 in the third trimester had serum amylase levels in excess of 100 mg. The highest serum amylase value recorded in our control subjects was 79.8 mg. of glucose per 100 ml.” In comparison, the highest amylase activities recorded in the pregnant patients were 78, 209, and 154 trimesters, mg. for the first, second, and third respectively. The mean serum amylase value + 2 S.E. computed for each of the 5 week periods between weeks 6 to 40 of pregnancy are plotted in Fig. 1. As may be seen, there was a progressive rise in serum amylase from weeks 6 to 25, followed by a gradual but less pronounced fall to the end of pregnancy. Statistically significant differences were found between the mean serum amylase values for the 6 to 10 and 11 to 15 week periods (p < O.OOl), and between the 16 to 20 and 21 to 25 week periods (p < 0.001). Supplementary data for the 5 week periods are given in Table I. Of special note is the percentage of patients in each period exhibiting values in excess of the presumptive top normal value of 100. As shown, none of the patients in the first 15 weeks had values above this level, whereas two-thirds of those in the 21 to 25 week period had values greater than this level. The isoamylase analysis in the selected high and low value samples during each of the trimesters gave “P”-type to “S”-type isoamylase ratios of 1 : 1 during the first trimester, 1:3 during the second
Volume Number
122 3
trimester, and 1: 1 during the third trimester. These limited data indicate the possibility of an alteration in the relative distribution of the isoamylases during the second trimester, with the S-type isoamylase dominating during this period. Comment
Aside from fundamental physiologic interest, knowledge of the levels and behavior of serum amylase during pregnancy has clinical relevance. The latter lies in the fact that clinical assessment of abdominal complaints that may be presented by pregnant women must be founded upon knowledge of the levels of serum amylase at any given time during pregnancy. Without such information, complicating pancreatic disease may be inappropriately diagnosed or mistakenly excluded; yet, the data at hand on this subject are not only sparse but in many ways are conflicting. Fitzgerald’ reported that the serum amylase levels during the early weeks of pregnancy tended to be low. More recently, Adlercreutz, Soininen, and Karkonen? described increased serum amylase levels during pregnancy without definition as to the duration of the pregnancy. De Castro, Gomez, and Spellacy” noted that there was a gradual rise in amylase during pregnancy, both in the maternal serum and in the amniotic fluid. At 36 weeks, however, amylase activity in the amniotic fluid rose steeply in contrast with the activities in maternal serum. Burt and McAlister” found that there was no significant difference in the level of serum amylase activity in pregnant women in the last trimester as compared with normal control women. They made no mention, however, of alterations occurring in this enzymatic activity during the first two trimesters. The data obtained by us in our study of 200 pregnant women in various stages of pregnancy indicated that there was a progressive rise in serum amylase activity until the twenty-fifth week of pregnancy. Thereafter, the serum amylase values tended to fall but still remained well above the values in the earlier stages of pregnancy. Of considerable clinical interest is the fact that, in a considerable number of these normal pregnant women in the second and third trimesters, serum amylase values were encountered that exceeded 100, the ostensible upper limit of normal. It is to be emphasized, therefore, that interpretation of seemingly elevated values for serum amylase in pregnant women in the second
Serum
amylase
changes
during
pregnancy
285
or third trimester who have abdominal pain and other upper abdominal symptoms must take into consideration the fact that serum amylase values in these trimesters may normally be as high as 200. The alteration in relative distribution of P-type to S-type isoamylase, with dominance of the S-type isoenzyme in the second trimester, is of interest. The pathogenesis and significance of the alteration, however, are presently obscure. Similar isoamylase analysis is now being made on all available specimens, rather than just on those with high and low values from each of the three trimesters. These data will form the basis for a separate report and hopefully will shed more light on the changes in pattern of serum amylase occurring during pregnancy. The reasons for the changes in serum amylase activity that were noted in our subjects are not altogether clear. Speculation regarding possible responsible mechanisms must certainly include consideration of the several endocrine and hormonal alterations that are known to take place during pregnancy. Just how these affect the serum amylase activity, however, is unknown. Thought should be given to the possibility that the changes in serum amylase activity during pregnancy may be related to preferential passage in some way from mother to fetus. Transplacental passage has been suggested.g, lo decastro, Gomez, and SpellacyY noted that an abrupt rise occurs in amniotic fluid amylase beginning about the thirty-sixth week of pregnancy. This sharp rise was unaccompanied by a parallel rise in amylase activity in the maternal blood. While this observation raises the possibility that maternal amylase may find its way into the amniotic fluid in the later stages of pregnancy, the finding by Wolf and Taussig13 that amylase zymograms of amniotic fluid were nearly identical to those of neonatal urine weighs against it. :\nother speculative consideration is that the amylase rise up to the twenty-fifth week and its fall thereafter may be in part the result of alterations in renal clearance rates for amylase. Of note in this regard is the increase in creatinine clearance observed to occur during pregnancy.ll Further, Kuhlbath and Widholml’ noted lesser values for serum creatinine in pregnant women as compared with nonpregnant subjects. They additionally noted that there was a progressive fall in serum creatinine during pregnancy, with the sharpest decline occurring in the second trimester.
REFERENCES
1. Fitzgerald, 0.: Br. Med. J. 1: 349, 1955. 2. Adlercreutz, H., Soininen, K., and Karkonen, M.: Br. Med. J. 2: 529, 1972. 3. decastro, A. F., Gomez, M. U., and Spellacy, W. M.: AM. J. OBSTET. GYNECOL. 116: 931, 1973. 4. Ahlert, G., Boehm, M., and Brueschke, G.: Experientia 25: 32, 1969. 5. Burt, R. L., and McAlister, J. A.: Obstet. Gynecol. 28: 351, 1966. 6. Berk, J. E., Smith, B. H., and Akrawi, M. A.: Am. J. Gastroenterol. 56: 216, 1971. 7. Fridhandler, L., and Berk, J. E.: Clin. Chem. 16: 911. 1970.
8. 9. 10. 11. 12. 13.
Fridhandler, L., Berk, J. E., and Ueda, M.: Ciin. Chem. 18: 1493, 1972. Ahlert, G., Hofer, E., and Ahlert, I.: Dtsch. Gesundh. Wochenschr. 23: 1599, 1968. Gautier, E., Gautier, R., and Richtreich, R.: Ifeiv. Paediatr. Acta 17: 415, 1962. Sims, E. A. H., and Krantz, K. E.: J. Clin. Invest. 37: 1764, 1958. Kuhlback, B., and Widholm, D.: Stand. J. Clin. Lab. Invest. 18: 654, 1966. Wolf, R. O., and Taussig, L. M.: Obstet. Gynecol. 41: 337, 1973.
KAISER,
EDWARD
LOUIS With
M.D.
BERK,
M.D.
FRIDHANDLER, the technical
PH.D.
assistance
KATHERINE
of
MONTGOMERY,
DEBORAH
WONG,
B.A
B.A.
Irvine, California Study
of the behavior of serum amylase activity in 200 pregnant women in various stages indicated that: (1) serum amylase rises gradually during pregnancy until the twenty-fifth week and thereafter falls slightly; (2) serum amylase values may be found in normal pregnant women during the second and third trimesters that exceed those in normal men and nonpregnant women; (3) during the second trimester of pregnancy there may be an alteration in the relative distribution of the pancreatic and salivary-type isoamylases with the salivary type tending to dominate. Knowledge of these changes is of importance in the clinical assessment of serum amylase values in pregnant women complaining of abdominal pain and other symptoms suggestive of complicating acute pancreatitis. An explanation for the observed changes is not readily available and further study is required. of pregnancy
Material
T H E L E V E L of serum amylase during pregnancy in human beings and in other animals has been reported differently by different observers.r+ Since some pregnant women develop abdominal pain and other symptoms that are clinically consistent with those associated with acute pancreatitis,6 it is of importance to know whether the serum amylase level found in such patients exceeds or is within the normal range. The study that forms the basis of this report was undertaken to help provide this information. From the Division of Gnstroenterology, Department of Medicine, University Irvine, Supported Foundation, Received Revised Accepted
by a grant Inc.
from
October
The John
California
A. Hartford Methods
for publication September
of
A total of 200 pregnant women attending the Prenatal Clinic of the Orange County Medical Center were selected for the purposes of this study. All of them were asymptomatic. None of them used any drugs other than prescribed vitamins, consumed alcohol more than occasionally or socially, smoked many cigarettes, or had a history of previous hepatic, gallstone, or pancreatic disease. Their ages ranged from 14 to 37 years. The group was comprised of white and black native Americans, as well as Americans of Mexican origin. Of the 200 women, 62 were in the first trimester of pregnancy, 78 were in the second trimester, and 60 were in the third trimester.
July
23, 1974.
A blood sample taken from each of the 200 subjects was examined for total serum amylase activity with an automated saccharogenic method.7 The reducing power generated is the measure of amylase activity and is expressed as milligrams of glucose per 100 ml. Certain samples obtained from subjects
12, 1974. 8, 1974.
Reprint requests: 1. Edward Berk, M.D., Department of Medicine, University of California, College of Medicine, Irvine, California 92664. 283
- _.,,.
Am. J. Obst .I
. 0
r’
140 -
8 -
130-
=
2 + :I S.E
..
IZO110 100 -
da ii 8 ? g
00 9070-
z
60 -
5 F ::
5040 -
z I
5
N=28
3020-
101 ,
N’42
N=24
N=28
N=25
N=28
N’24
,
,
,
,
,
21-25
26-X)
31-35
36-40
,
6-10
II-15
16-20
DURATION
OF PREGNANCY
(WEEKS)
Fig. 1. Mean ? 2 S.E. values for serum amylase during pregnancy. (N refers to number of patients in each 5 week period.)
Table I. Serum
amylase
6-10 11-15 16-20 21-25 26-30 31-35 36-40
during
activity studied
pregnancy
I
I
Serum amylase values (mg. of gIuAxe/lOO ml.)
I
I
I
I Weeksof pregnancy
values
I
I
28 42 24 28 25 28 25
27 24 52 54 58 57 52
I > 100
I
/N.-“lL~~-“‘..:-(,,..~ patients
S.E. 68 100 117 209 208 136 154
46 63 84 117 106 92 84
,
1.8 2.3 3.5 6.7 8.0 3.7 3.9
i$io 0 0 6 18 10 9 3
0 0 25 64 40 32 13
200
in each of the trimesters of pregnancy were selected for isoamylase analysis. The samples selected for this analysis were those showing high or low values of amylase activity as compared to the rest of the group in the respective trimester. Two of the samples examined were from patients in the first trimester of pregnancy, three were from patients in the second trimester, and three were from patients in the third trimester. The isoamylase pattern in each of these samples was determined by means of a chromatographic technique previously reported from this laboratory.*
~-.--,
:.,,I, I / 1
Results The serum amylase results of an earlier stud) made by us8 in a small group of 30 subject\ c’omposed of apparently normal men and nonpregnant women were recalculated. To help insure a normal distribution, each value was converted intc; its logarithm and the mean and standard deviation of these logarithms were calculated. The results indicated that a serum activity of 100 mg. of glucose per 100 ml. might better be considered the upper limit of normal rather than the level of 90 mg. of glucose per 100 ml. previously suggested.” By contrast with this value, the amylase value (mean + SE.), computed for each of the trimesters, rose from 52 rt 1.6 in the 62 patients in the first trimester, to 103 ? 4.0 in the 78 patients in the second trimester, and then diminished to 100 + 12.2 in the 60 patients in the third trimester. Corollary to this change in mean values was the fact that none of the 62 patients in the first trimester, 33 (42 per cent) of the 78 in the second trimester, and 13 (22 per cent) of the 60 in the third trimester had serum amylase levels in excess of 100 mg. The highest serum amylase value recorded in our control subjects was 79.8 mg. of glucose per 100 ml.” In comparison, the highest amylase activities recorded in the pregnant patients were 78, 209, and 154 trimesters, mg. for the first, second, and third respectively. The mean serum amylase value + 2 S.E. computed for each of the 5 week periods between weeks 6 to 40 of pregnancy are plotted in Fig. 1. As may be seen, there was a progressive rise in serum amylase from weeks 6 to 25, followed by a gradual but less pronounced fall to the end of pregnancy. Statistically significant differences were found between the mean serum amylase values for the 6 to 10 and 11 to 15 week periods (p < O.OOl), and between the 16 to 20 and 21 to 25 week periods (p < 0.001). Supplementary data for the 5 week periods are given in Table I. Of special note is the percentage of patients in each period exhibiting values in excess of the presumptive top normal value of 100. As shown, none of the patients in the first 15 weeks had values above this level, whereas two-thirds of those in the 21 to 25 week period had values greater than this level. The isoamylase analysis in the selected high and low value samples during each of the trimesters gave “P”-type to “S”-type isoamylase ratios of 1 : 1 during the first trimester, 1:3 during the second
Volume Number
122 3
trimester, and 1: 1 during the third trimester. These limited data indicate the possibility of an alteration in the relative distribution of the isoamylases during the second trimester, with the S-type isoamylase dominating during this period. Comment
Aside from fundamental physiologic interest, knowledge of the levels and behavior of serum amylase during pregnancy has clinical relevance. The latter lies in the fact that clinical assessment of abdominal complaints that may be presented by pregnant women must be founded upon knowledge of the levels of serum amylase at any given time during pregnancy. Without such information, complicating pancreatic disease may be inappropriately diagnosed or mistakenly excluded; yet, the data at hand on this subject are not only sparse but in many ways are conflicting. Fitzgerald’ reported that the serum amylase levels during the early weeks of pregnancy tended to be low. More recently, Adlercreutz, Soininen, and Karkonen? described increased serum amylase levels during pregnancy without definition as to the duration of the pregnancy. De Castro, Gomez, and Spellacy” noted that there was a gradual rise in amylase during pregnancy, both in the maternal serum and in the amniotic fluid. At 36 weeks, however, amylase activity in the amniotic fluid rose steeply in contrast with the activities in maternal serum. Burt and McAlister” found that there was no significant difference in the level of serum amylase activity in pregnant women in the last trimester as compared with normal control women. They made no mention, however, of alterations occurring in this enzymatic activity during the first two trimesters. The data obtained by us in our study of 200 pregnant women in various stages of pregnancy indicated that there was a progressive rise in serum amylase activity until the twenty-fifth week of pregnancy. Thereafter, the serum amylase values tended to fall but still remained well above the values in the earlier stages of pregnancy. Of considerable clinical interest is the fact that, in a considerable number of these normal pregnant women in the second and third trimesters, serum amylase values were encountered that exceeded 100, the ostensible upper limit of normal. It is to be emphasized, therefore, that interpretation of seemingly elevated values for serum amylase in pregnant women in the second
Serum
amylase
changes
during
pregnancy
285
or third trimester who have abdominal pain and other upper abdominal symptoms must take into consideration the fact that serum amylase values in these trimesters may normally be as high as 200. The alteration in relative distribution of P-type to S-type isoamylase, with dominance of the S-type isoenzyme in the second trimester, is of interest. The pathogenesis and significance of the alteration, however, are presently obscure. Similar isoamylase analysis is now being made on all available specimens, rather than just on those with high and low values from each of the three trimesters. These data will form the basis for a separate report and hopefully will shed more light on the changes in pattern of serum amylase occurring during pregnancy. The reasons for the changes in serum amylase activity that were noted in our subjects are not altogether clear. Speculation regarding possible responsible mechanisms must certainly include consideration of the several endocrine and hormonal alterations that are known to take place during pregnancy. Just how these affect the serum amylase activity, however, is unknown. Thought should be given to the possibility that the changes in serum amylase activity during pregnancy may be related to preferential passage in some way from mother to fetus. Transplacental passage has been suggested.g, lo decastro, Gomez, and SpellacyY noted that an abrupt rise occurs in amniotic fluid amylase beginning about the thirty-sixth week of pregnancy. This sharp rise was unaccompanied by a parallel rise in amylase activity in the maternal blood. While this observation raises the possibility that maternal amylase may find its way into the amniotic fluid in the later stages of pregnancy, the finding by Wolf and Taussig13 that amylase zymograms of amniotic fluid were nearly identical to those of neonatal urine weighs against it. :\nother speculative consideration is that the amylase rise up to the twenty-fifth week and its fall thereafter may be in part the result of alterations in renal clearance rates for amylase. Of note in this regard is the increase in creatinine clearance observed to occur during pregnancy.ll Further, Kuhlbath and Widholml’ noted lesser values for serum creatinine in pregnant women as compared with nonpregnant subjects. They additionally noted that there was a progressive fall in serum creatinine during pregnancy, with the sharpest decline occurring in the second trimester.
REFERENCES
1. Fitzgerald, 0.: Br. Med. J. 1: 349, 1955. 2. Adlercreutz, H., Soininen, K., and Karkonen, M.: Br. Med. J. 2: 529, 1972. 3. decastro, A. F., Gomez, M. U., and Spellacy, W. M.: AM. J. OBSTET. GYNECOL. 116: 931, 1973. 4. Ahlert, G., Boehm, M., and Brueschke, G.: Experientia 25: 32, 1969. 5. Burt, R. L., and McAlister, J. A.: Obstet. Gynecol. 28: 351, 1966. 6. Berk, J. E., Smith, B. H., and Akrawi, M. A.: Am. J. Gastroenterol. 56: 216, 1971. 7. Fridhandler, L., and Berk, J. E.: Clin. Chem. 16: 911. 1970.
8. 9. 10. 11. 12. 13.
Fridhandler, L., Berk, J. E., and Ueda, M.: Ciin. Chem. 18: 1493, 1972. Ahlert, G., Hofer, E., and Ahlert, I.: Dtsch. Gesundh. Wochenschr. 23: 1599, 1968. Gautier, E., Gautier, R., and Richtreich, R.: Ifeiv. Paediatr. Acta 17: 415, 1962. Sims, E. A. H., and Krantz, K. E.: J. Clin. Invest. 37: 1764, 1958. Kuhlback, B., and Widholm, D.: Stand. J. Clin. Lab. Invest. 18: 654, 1966. Wolf, R. O., and Taussig, L. M.: Obstet. Gynecol. 41: 337, 1973.
