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The effect of pregnancy upon urinary mucopolysaccharide excretion
The effect of pregnancy upon urinary mucopolysaccharide GEORGE LUCAS
R. DE
WILLIAM Ann
Arbor
excretion
THOMPSON, VRIES, J.
M.D. M.S.
LEDGER,
and Eloise,
M.D.,
F.A.C.O.G.
Michigan
One hundred and six 24 hour urine samples were obtained from 6 women during the antepartum and postpartum periods. In 96 of the specimens in which the total urinary creatinine was 800 mg. or greater, total mucopolysaccharide (MPS) excretion was determined. Fifty-nine of the determinations exceeded the upper limits of normal, with the elevations usually noted beyond the twentieth week of pregnancy and in the postpartum period. All 106 MPS determinations were extrapolated to a creatine of I .O Gm. Thirty-nine of the MPS-creatinine ratios exceeded the limits of normal, and most of these occurred in the last 20 weeks of pregnancy and in the immediate postpartum period. Possible mechanisms and the significance of elevated MPS excretion during pregnancy are discussed.
Material
I N A P R E v 10 u s evaluation, it was noted that 24 hour urinary mucopolysaccharides, or glycosaminoglycans (MPS) , were elevated during pregnancy and in the postpartum period in individual samples from a few women.’ In order to delineate the pattern, if any, of MPS excretion in pregnancy, a detailed study of the urinary excretion of MPS was performed on 6 patients.
Supported in part by United States Public Health Service Grant AM 09796. a Wayne County General Hospital ’ Research and Education Fund Grant, and a grant from The Upjohn Co., Kalamazoo, Michigan.
Accepted
for publication January
November
methods
Twenty-four-hour urine samples were collected from patients on the obstetric service of the University of Michigan Medical Center. One hundred and six urine samples were obtained from 6 patients during the antepartum and postpartum periods. These patients were all white and upper-middle class, in most cases the wives of residents at the University of Michigan MedicaI Center. Generally, they were interested in the study being done and cooperated fully in both the outpatient and inpatient collection of 24 hour urine specimens. All of these women were delivered of mature infants and none had any evidence of a serious postpartum infection. Two of the 6 patients were delivered of their infants by elective repeat cesarean section. MPS and creatinine determinations were made on the 106 urine specimens. In 10 of the specimens, the total urinary creatinine was less than 800 mg., in which case the MPS determinations were not included in the tabulations. A MPS-creatinine ratio was calculated, with the use of a creatinine value
From the Department of Medicine, Wayne County General Hospital, and the Department of Obstetrics and Gynecology, The University of Michigan.
y;;;foed
and
20,
14, 1974.
Reprint requests: Dr. William J. Ledger, Department of Obstetrics-Gynecology, Los Angeles County/University of Southern California Medical Center, 1240 N. Mission Road, Los Angeles, Califorma 90033. 1069
1070
Thompson,
de Vies,
30
and
August 15, 1974 Am. J. Obstet. Gynecol.
Ledger
r
Fig. 1. The effect of pregnancy on MPS excretion.
of one as the standard. This calculation was done on all 106 samples. MPS was precipitated from the 24 hour urine specimens with cetylpyridinium chloride by a previously described method from our laboratory.” Following reprecipitation. MPS was measured as uranic acid with the carbozol reaction. The creatinine content of each urine sample was also determined, by a modification’ of the Jaffe reaction. With the use of data available from normal nonpregnant women, the mean 24 hour urinary MPS excretion, when the creatinine was greater than 0.8, was 7.05 mg., with the upper boundary of normal at 9.18 mg. By means of a computer, the 24 hour MPS excretion was extrapolated (or “normalized”) to that value calculated to have occurred if the 24 hour creatinine excretion had been 1.0 Gm. This was done to eliminate differences in urine collection, urine flow, and the ranges of normal renal function-creatinine excretion and thus renal blood flow. When the MPS excretion is thus normalized against a creatinine of 1.0, the mean is 7.6 mg., with an upper boundary of 11.52 mg. Results
The rrsults of the total urinary MPS excretion in 96 antepartum and postpartum determinations are graphically portrayed in Fig. 1. Fifty-nine of the determinations exceeded the upper limits of normal while 37 were within statistical norms. The in-
crease in MPS excretion rate is most marked after the twentieth week of pregnancy and rapidly falls to normal limits in the postpartum period. The highest single MPS total is noted in the postpartum period in a patient who had undergone cesarean section. The MPS-creatinine ratio is depicted in Fig. 2. Thirty-nine of the 106 determinations exceeded normal limits while 67 were within normal limits. There is a rise in MPS escretion in the last portion of pregnancy that rapidly returns to normal in the postpartum period. The highest values of MPS excretion were seen in the early postpartum period in those patients who had undergone cesarean section. Comment
This intens& evaluation of 6 pregnant patients yielded a clearer picture of the influence of pregnancy upon urinary MPS excretion than previously available from a fer\. scattered 24 hour urine samples from pregnant \vomen.’ In retrospect, most of the earlier 24 hour urine specimens with elevatrd MPS values were obtained from women in the third trimester of pregnancy and distorted the nature of the changes in excretion during pregnancy. In the MPS present study, most of the elevations were noted beyond the twentieth week of pregnancy. A study like this, with the collection of many separate urinary samples from women throughout pregnancy, required the
Volume 119 Number 8
Pregnancy
o POSTPARTUM
CESAREAN
1071
SECTlON
Fig. 2. The effect of pregnancy upon the MPWcreatinine
cooperation of motivated women, who had sought antepartum care early in pregnancy and were willing to make frequent 24 hour urine collections as an outpatient. The influence of social class, maternal nutritional status, or pregnancy complications upon MPS excretion was not clarified by this report. The data indicate that pregnancy is accompanied by an increase in urinary MPS excretion (see Fig. 1). This increase parallels to some extent the increased urinary creatinine clearance, for the MPS excretion increase was not as great when corrected to a creatinine value of one. Despite this correction, the trend of increasing MPS excretion during the later phases of pregnancy was still obvious (see Fig. 2). Elevated MPS excretion values were seen in the immediate postpartum period, with the highest values in women who had a cesarean section. These elevated MPS values returned to normal levels in the later postpartum period. There are a number of possible mechanisms for the increase in urinary MPS excretion during pregnancy and the postpartum period. MPS excretion levels reflect ground substance turnover, including synthesis and breakdown of connective tissue. For example, an increase in the urinary excretion of MPS
and MPS excretion
ratio.
has been found in patients with connective tissue disease, such as Hurler’s syndrome,4 rheumatoid arthritis,5 systemic lupus erythematosus,G and Marfan’s syndrome.? The increased MPS excretion during pregnancy probably reflects new ground substance formation, for the higher values parallel increased uterine, placental, and fetal growth. An assessment of the contribution of each of these components to the elevated MPS excretion is not possible from this study. In the postpartum period, involution of the uterus seems to be an important contributor to the elevated MPS excretion. The highest levels of MPS excretion followed a major operative procedure directly involving the uterus, the cesarean section. This increase following cesarean section is more than the response to a major operation, for a previous study noted lower MPS excretion rates with another major operation, the cesarean hysterectomy, in which the uterine contribution to MPS excretion was lost1 The clinical significance of this elevated MPS excretion during pregnancy is not known at the present time. To date, only uncomplicated pregnancies have been studied in detail. If urinary MPS excretion is altered by abnormal pregnancy states, this determination might be of some clinical value.
1072
Thompson,
de
Vries,
and
Ledger
REFERENCES
1. Ledger, W. J., Thompson, G. R., and Grobelny, S. L.: AM. J. OBSTET. GYSECOL. 110: 494, 1971. 2. Thompson, G. R., Castor, C. W., Ballantyne, L. M., and Prince, R. K.: J. Lab. Clin. Med. 68: 617, 1966. 3. Bonsnes, R. W., and Tansskey, H. H.: J. Biol. Chem. 158: 581, 1945.
4. ci 6. 7.
Dorfman, A., and Matalon, R.: Am. J. Med. 47: 691, 1969. Di Ferrante, N.: J. Clin. Invest. 36: 1516, 1957. Di Ferrante, N., Robbins, W. C., and Rich, C.: J. Lab. Clin. Med. 50: 897, 1957. G. S., and Dalferes, E. R., Jr.: Berenson, Clin. Res. 11: 57, 1963.
R. DE
WILLIAM Ann
Arbor
excretion
THOMPSON, VRIES, J.
M.D. M.S.
LEDGER,
and Eloise,
M.D.,
F.A.C.O.G.
Michigan
One hundred and six 24 hour urine samples were obtained from 6 women during the antepartum and postpartum periods. In 96 of the specimens in which the total urinary creatinine was 800 mg. or greater, total mucopolysaccharide (MPS) excretion was determined. Fifty-nine of the determinations exceeded the upper limits of normal, with the elevations usually noted beyond the twentieth week of pregnancy and in the postpartum period. All 106 MPS determinations were extrapolated to a creatine of I .O Gm. Thirty-nine of the MPS-creatinine ratios exceeded the limits of normal, and most of these occurred in the last 20 weeks of pregnancy and in the immediate postpartum period. Possible mechanisms and the significance of elevated MPS excretion during pregnancy are discussed.
Material
I N A P R E v 10 u s evaluation, it was noted that 24 hour urinary mucopolysaccharides, or glycosaminoglycans (MPS) , were elevated during pregnancy and in the postpartum period in individual samples from a few women.’ In order to delineate the pattern, if any, of MPS excretion in pregnancy, a detailed study of the urinary excretion of MPS was performed on 6 patients.
Supported in part by United States Public Health Service Grant AM 09796. a Wayne County General Hospital ’ Research and Education Fund Grant, and a grant from The Upjohn Co., Kalamazoo, Michigan.
Accepted
for publication January
November
methods
Twenty-four-hour urine samples were collected from patients on the obstetric service of the University of Michigan Medical Center. One hundred and six urine samples were obtained from 6 patients during the antepartum and postpartum periods. These patients were all white and upper-middle class, in most cases the wives of residents at the University of Michigan MedicaI Center. Generally, they were interested in the study being done and cooperated fully in both the outpatient and inpatient collection of 24 hour urine specimens. All of these women were delivered of mature infants and none had any evidence of a serious postpartum infection. Two of the 6 patients were delivered of their infants by elective repeat cesarean section. MPS and creatinine determinations were made on the 106 urine specimens. In 10 of the specimens, the total urinary creatinine was less than 800 mg., in which case the MPS determinations were not included in the tabulations. A MPS-creatinine ratio was calculated, with the use of a creatinine value
From the Department of Medicine, Wayne County General Hospital, and the Department of Obstetrics and Gynecology, The University of Michigan.
y;;;foed
and
20,
14, 1974.
Reprint requests: Dr. William J. Ledger, Department of Obstetrics-Gynecology, Los Angeles County/University of Southern California Medical Center, 1240 N. Mission Road, Los Angeles, Califorma 90033. 1069
1070
Thompson,
de Vies,
30
and
August 15, 1974 Am. J. Obstet. Gynecol.
Ledger
r
Fig. 1. The effect of pregnancy on MPS excretion.
of one as the standard. This calculation was done on all 106 samples. MPS was precipitated from the 24 hour urine specimens with cetylpyridinium chloride by a previously described method from our laboratory.” Following reprecipitation. MPS was measured as uranic acid with the carbozol reaction. The creatinine content of each urine sample was also determined, by a modification’ of the Jaffe reaction. With the use of data available from normal nonpregnant women, the mean 24 hour urinary MPS excretion, when the creatinine was greater than 0.8, was 7.05 mg., with the upper boundary of normal at 9.18 mg. By means of a computer, the 24 hour MPS excretion was extrapolated (or “normalized”) to that value calculated to have occurred if the 24 hour creatinine excretion had been 1.0 Gm. This was done to eliminate differences in urine collection, urine flow, and the ranges of normal renal function-creatinine excretion and thus renal blood flow. When the MPS excretion is thus normalized against a creatinine of 1.0, the mean is 7.6 mg., with an upper boundary of 11.52 mg. Results
The rrsults of the total urinary MPS excretion in 96 antepartum and postpartum determinations are graphically portrayed in Fig. 1. Fifty-nine of the determinations exceeded the upper limits of normal while 37 were within statistical norms. The in-
crease in MPS excretion rate is most marked after the twentieth week of pregnancy and rapidly falls to normal limits in the postpartum period. The highest single MPS total is noted in the postpartum period in a patient who had undergone cesarean section. The MPS-creatinine ratio is depicted in Fig. 2. Thirty-nine of the 106 determinations exceeded normal limits while 67 were within normal limits. There is a rise in MPS escretion in the last portion of pregnancy that rapidly returns to normal in the postpartum period. The highest values of MPS excretion were seen in the early postpartum period in those patients who had undergone cesarean section. Comment
This intens& evaluation of 6 pregnant patients yielded a clearer picture of the influence of pregnancy upon urinary MPS excretion than previously available from a fer\. scattered 24 hour urine samples from pregnant \vomen.’ In retrospect, most of the earlier 24 hour urine specimens with elevatrd MPS values were obtained from women in the third trimester of pregnancy and distorted the nature of the changes in excretion during pregnancy. In the MPS present study, most of the elevations were noted beyond the twentieth week of pregnancy. A study like this, with the collection of many separate urinary samples from women throughout pregnancy, required the
Volume 119 Number 8
Pregnancy
o POSTPARTUM
CESAREAN
1071
SECTlON
Fig. 2. The effect of pregnancy upon the MPWcreatinine
cooperation of motivated women, who had sought antepartum care early in pregnancy and were willing to make frequent 24 hour urine collections as an outpatient. The influence of social class, maternal nutritional status, or pregnancy complications upon MPS excretion was not clarified by this report. The data indicate that pregnancy is accompanied by an increase in urinary MPS excretion (see Fig. 1). This increase parallels to some extent the increased urinary creatinine clearance, for the MPS excretion increase was not as great when corrected to a creatinine value of one. Despite this correction, the trend of increasing MPS excretion during the later phases of pregnancy was still obvious (see Fig. 2). Elevated MPS excretion values were seen in the immediate postpartum period, with the highest values in women who had a cesarean section. These elevated MPS values returned to normal levels in the later postpartum period. There are a number of possible mechanisms for the increase in urinary MPS excretion during pregnancy and the postpartum period. MPS excretion levels reflect ground substance turnover, including synthesis and breakdown of connective tissue. For example, an increase in the urinary excretion of MPS
and MPS excretion
ratio.
has been found in patients with connective tissue disease, such as Hurler’s syndrome,4 rheumatoid arthritis,5 systemic lupus erythematosus,G and Marfan’s syndrome.? The increased MPS excretion during pregnancy probably reflects new ground substance formation, for the higher values parallel increased uterine, placental, and fetal growth. An assessment of the contribution of each of these components to the elevated MPS excretion is not possible from this study. In the postpartum period, involution of the uterus seems to be an important contributor to the elevated MPS excretion. The highest levels of MPS excretion followed a major operative procedure directly involving the uterus, the cesarean section. This increase following cesarean section is more than the response to a major operation, for a previous study noted lower MPS excretion rates with another major operation, the cesarean hysterectomy, in which the uterine contribution to MPS excretion was lost1 The clinical significance of this elevated MPS excretion during pregnancy is not known at the present time. To date, only uncomplicated pregnancies have been studied in detail. If urinary MPS excretion is altered by abnormal pregnancy states, this determination might be of some clinical value.
1072
Thompson,
de
Vries,
and
Ledger
REFERENCES
1. Ledger, W. J., Thompson, G. R., and Grobelny, S. L.: AM. J. OBSTET. GYSECOL. 110: 494, 1971. 2. Thompson, G. R., Castor, C. W., Ballantyne, L. M., and Prince, R. K.: J. Lab. Clin. Med. 68: 617, 1966. 3. Bonsnes, R. W., and Tansskey, H. H.: J. Biol. Chem. 158: 581, 1945.
4. ci 6. 7.
Dorfman, A., and Matalon, R.: Am. J. Med. 47: 691, 1969. Di Ferrante, N.: J. Clin. Invest. 36: 1516, 1957. Di Ferrante, N., Robbins, W. C., and Rich, C.: J. Lab. Clin. Med. 50: 897, 1957. G. S., and Dalferes, E. R., Jr.: Berenson, Clin. Res. 11: 57, 1963.