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Measurement of fetal urine production in normal pregnancy by real-time ultrasonography
Measurement of fetal urine production in normal pregnancy by real-time ultrasonography Ron Rabinowitz, MD, Mark T. Peters, MD, Sanjay Vyas, MD, Stuart Campbell, MD, and Kypros H. Nicolaides, MD London, England Serial measurements of fetal bladder volume were obtained by real-time ultrasonography at 2- to 5-minute intervals, and the hourly fetal urine production rate was calculated. The mean hourly fetal urine production rate increased from 5 mllhr at 20 weeks' gestation to 51 mllhr at 40 weeks. These values are double those reported in previous studies that measured fetal bladder volumes at 15- to 30-minute intervals because the cycle length is shorter than previously thought. (AM J OBSTET GVNECOL 1989;161 :1264-6.)
Key words: Ultrasonography, fetal urine production, amniotic fluid volume Fetal urine production can be estimated by computing serial measurements of fetal bladder volume with time. Such studies have documented that hourly fetal urine production rate in normal pregnancy increases with gestational age. 1·4 However, these studies were performed with static scanners and bladder measurements were made at 15- to 30-minute intervals. With the introduction of real-time ultrasonography it is now possible to image fetal activity continuously and to make more frequent measurements of the fetal bladder. The purpose of this study was to use real-time scanning to evaluate micturition in the normal fetus.
Patients and methods Eighty-five consecutive healthy women with a normal singleton pregnancy at 20 to 41 weeks' gestation were recruited from the King's College Hospital routine antenatal clinic. Fetal urine studies were performed once in each patient. Gestational age was determined by N aegele's rule and confirmed by an ultrasonographic scan at 18 to 20 weeks. All fetuses were anatomically normal. Subsequently, 81 of the women were delivered at term of normal infants of appropriate weight for gestation (mean, 3.19 kg; range, 2.5 to 4.4 kg); there was one unexplained stillbirth. Two patients were delivered at 36 weeks, one at 35 weeks, and one at 32 weeks' gestation. Seventy-eight (92 %) women were delivered vaginally and seven were delivered by cesarean section (three for intrapartum fetal distress and four for cephalopelvic disproportion). From the Hams Birthnght Research Centre for Fetal MediCine, Department of Obstetncs and Gynaecology, Kings College School of Medicine. Received for publication January 3, 1989; revised May 10, 1989; accepted May 16, 1989. Reprint requests: Kypros H. Nzeolaldes, MD , Kings College School of MediclTU', Denmark Hill, London, England SE5 BRX. 6/1113999
1264
With the mothers in the semirecumbent pOSItion, real-time ultrasonography (3,5 MHz transducer, Hitachi EUB340) was used to obtain serial measurements of the fetal bladder. Measurements were made with electronic calipers at 2- to 5-minute intervals for a period of 1 hour. Time was recorded with a stopwatch. First, the greatest longitudinal axis was identified and measured . Then the transducer was rotated 90 degrees and the bladder was scanned superiorly and inferiorly to find the largest transverse section, which was used to obtain the transverse and anteroposterior diameters (Tl and T2, respectively). The time interval between longitudinal axis and transverse axis measurements was 30 to 60 seconds. The end of a cycle was defined either by the observation of micturition or by the observation of dynamic changes in the bladder including reduction in lumen size and increase in wall thickness. The volume immediately before the end of the cycle was defined as the maximum bladder volume. Bladder volume was calculated from the three measured diameters by means of the formula for an ovoid sphere (4/3 'IT x Ll2 x T1I2 x T2/2 where L is the greatest longitudinal axis). For each study 15 to 20 such measurements were obtained. The corresponding time for each volume was the mean value of the time recorded at measurement of the longitudinal diameter and the time at measurement of the transverse diameters. For each fetus all volume measurements were plotted against time, and the hourly fetal urine production rate was calculated by regression analysis of all the bladder volumes during the filling phase of the first cycle (Fig. 1). In 42 patients a complete cycle was observed, and the time interval between the end of one cycle and the end of the next was recorded. Regression analysis (P. Royston's statistical package for personal computers, Tiberlake Clark Limited, London) was used to calculate the mean and individual 95%
Fetal urine production
Volume 161 Number 5
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Fig. 1. Fetal bladder volume measurements at 2- to 5-minute intervals. The slope of the filling phase, calculated by regression analysis, is used to estimate the hourly fetal urine production rate. If measurements are taken at 30-minute intervals, the slope of the apparent filling phase would be less and the hourly fetal urine production rate would be approximately half the actual value. confidence intervals of hourly fetal urine production rate and maximum bladder volume for gestational age. The data for hourly fetal urine production rate were normalized by log transformation before regression analysis was performed.
Results The hourly fetal urine production rate was calculated in all 85 patients; however, maximum bladder volumes were obtained for only 81 of the fetuses. Emptying of the fetal bladder was visualized on 101 occasions and in each case occurred in <30 seconds. In 28 cases emptying was complete, and in 55 cases the residual bladder volume was less than 25%; in 16 cases it was 26% to 50% of the maximum bladder volume. In two cases fetal micturition was observed and the residual volume was 60% and 65% of the maximum bladder volume, respectively. The hourly fetal urine production rate increases with advancing gestation from a mean value of 5 ml/hr at 20 weeks' gestation to 56 ml/hr at 41 weeks' gestation [Fig. 2; r = 0.853, n = 85,p < 0.0001, log 10 (hourly fetal urine production rate + 3) = 0.088 + 0.041 X weeks' gestation, SD = 0.169]. The maximum bladder volume increases with gestation from a mean value of 1 ml at 20 weeks' gestation to 36 ml at 41 weeks [r = 0.911, n = 81, P < 0.0001, log 10 (maximum bladder volume + 9) = 0.377 + 0.031 x weeks' gestation, SD = 0.094]. The mean time for the 42 complete cycles was 25 minutes (range, 7 to 43 minutes), and this did not change significantly with gestation (r = 0.191). In 24 cases there were two consecutive filling phases in which the hourly fetal urine production rate for each bladder filling was calculated. These were
25
30
Gestation
35
40
(wk)
Fig. 2. Reference range (mean and individual 95% confidence intervals) of the hourly fetal urine production rate.
compared by Student's paired t test (mean = 30.3 mllhr, SD = 25.8 and mean = 29.7 mllhr, SD = 25.7, respectively); there was no significant difference.
Comment The rate of fetal urine production increases with gestation, and the hourly fetal urine production rate is approximately double that reported in previous studies (Table I). ' -5 Furthermore, there is no apparent decrease of hourly fetal urine production rate near term as suggested by Wladimiroff and Campbell! The most likely reason for the disparity in results between this and previous studies is that the cycle length is shorter than the mean of 110 minutes reported by Campbell et al.' This point is illustrated in Fig. 1 in which calculation of the hourly fetal urine production rate from bladder volume measurements at 15- to 3D-minute intervals is half the value obtained from measurements taken every 2 to 5 minutes. The urine production rate of the fetus at term is considerably greater than that of the neonate (1 to 2 mllkg/hr). This may be because the insensible loss in the neonate is substantially greater than that of the fetus , which is surrounded by fluid. Furthermore, if unimpaired placental transfer is assumed, the fetus has a continuous supply of free water, whereas in the neonate the supply of fluid is restricted to feeding times. Real-time ultrasonography has also allowed observations of fetal micturition and dynamic changes in bladder volume. Although studies with static scanners had suggested that bladder emptying may either occur over a few seconds or as a stepwise process over a period of 30 minutes,' this study indicates that under real-time imaging the bladder empties quickly in all cases. Previous studies used the method of Campbell et al.' to estimate hourly fetal urine production rate and reported that (1) in normal pregnancies there may be a diurnal variation in HFUPR; (2) in pregnancies complicated by fetal growth retardation the hourly fetal
1266 Rabinowitz at al.
November 1989 Am J Obstet Gynecol
Table I. Comparison of mean hourly fetal urine production rate (ml) at given gestational ages from various studies Gestational age (wk) Study Campbell et al.I Wladimiroff and Campbe1l2 Van Otterlo et aJ.3 Kurjak et aI.' Deutinger et aI.' Present study
20
5
40
9
4 6 14
urine production rate is decreased, whereas in pregnancies with maternal diabetes mellitus it is unchanged; and in (3) pregnancies complicated by idiopathic polyhydramnios the hourly fetal urine production rate can be decreased by maternal administration of indomethacin. The validity of these findings requires reevaluation by means of the methodology described in this study. 1 9 0
REFERENCES 1. Campbell S, Wladimiroff jW, Dewhurst CJ. The antenatal measurement of fetal urine production. j Obstet Gynaecol Br Commonw 1973;80:680-6. 2. Wladimiroff jW, Campbell S. Fetal urine-production rates in normal and complicated pregnancy. Lancet 1974; 1: 151-4. 3. Van Otterlo LC, Wladimiroff jW, Wallenburg HCS. Relationship between fetal urine production and amniotic fluid volume in normal pregnancy and pregnancy complicated by diabetes. Br j Obstet Gynaecol 1977;84:205-9.
10 8 8 8 18
12 12 12 10 12 22
15 15 15 12 14 27
18 18 18 14 18 33
23 24 23 19 20 41
28 27 26 26 22 51
4. Kurjak A, Kirkinen P, Latin V, Ivankovic D. Ultrasonic assessment of fetal kidney function in normal and complicated pregnancies. AM j OBSTET GYNECOL 1981; 141: 266-70. 5. Deutinger j, Bartl W, Pfersmann C, Neumark j, Bernaschek G. Fetal kidney volume and urine production in cases of fetal growth retardation. j Perinat Med 1987;15:30715. 6. Wladimiroff jW, Van Otterlo LC, Wallenburg HCS, Drogendijk AC. A combined ultrasonic and biochemical study of fetal renal function in the term fetus. Eur j Obstet Gynecol Reprod Bioi 1976;6:103-8. 7. Wladimiroff jW, Barentsen R, Wallenburg HCS, Drogendijk AC. Fetal urine production in a case of diabetes associated with polyhydramnios. Obstet Gynecol 1975;46: 100-2. 8. Kirshon B, Cotton DB. Polyhydramnios associated with a ring chromosome and low maternal serum u-fetoprotein levels managed with indomethacin. AM j OBSTET GYNECOL 1988; 158: 1063-4. 9. Chamberlain PF, Manning FA, Morrison I, Lange IR. Circadian rhythm in bladder volumes in the term human fetus. Obstet Gynecol 1984;64:657-60.
Key words: Ultrasonography, fetal urine production, amniotic fluid volume Fetal urine production can be estimated by computing serial measurements of fetal bladder volume with time. Such studies have documented that hourly fetal urine production rate in normal pregnancy increases with gestational age. 1·4 However, these studies were performed with static scanners and bladder measurements were made at 15- to 30-minute intervals. With the introduction of real-time ultrasonography it is now possible to image fetal activity continuously and to make more frequent measurements of the fetal bladder. The purpose of this study was to use real-time scanning to evaluate micturition in the normal fetus.
Patients and methods Eighty-five consecutive healthy women with a normal singleton pregnancy at 20 to 41 weeks' gestation were recruited from the King's College Hospital routine antenatal clinic. Fetal urine studies were performed once in each patient. Gestational age was determined by N aegele's rule and confirmed by an ultrasonographic scan at 18 to 20 weeks. All fetuses were anatomically normal. Subsequently, 81 of the women were delivered at term of normal infants of appropriate weight for gestation (mean, 3.19 kg; range, 2.5 to 4.4 kg); there was one unexplained stillbirth. Two patients were delivered at 36 weeks, one at 35 weeks, and one at 32 weeks' gestation. Seventy-eight (92 %) women were delivered vaginally and seven were delivered by cesarean section (three for intrapartum fetal distress and four for cephalopelvic disproportion). From the Hams Birthnght Research Centre for Fetal MediCine, Department of Obstetncs and Gynaecology, Kings College School of Medicine. Received for publication January 3, 1989; revised May 10, 1989; accepted May 16, 1989. Reprint requests: Kypros H. Nzeolaldes, MD , Kings College School of MediclTU', Denmark Hill, London, England SE5 BRX. 6/1113999
1264
With the mothers in the semirecumbent pOSItion, real-time ultrasonography (3,5 MHz transducer, Hitachi EUB340) was used to obtain serial measurements of the fetal bladder. Measurements were made with electronic calipers at 2- to 5-minute intervals for a period of 1 hour. Time was recorded with a stopwatch. First, the greatest longitudinal axis was identified and measured . Then the transducer was rotated 90 degrees and the bladder was scanned superiorly and inferiorly to find the largest transverse section, which was used to obtain the transverse and anteroposterior diameters (Tl and T2, respectively). The time interval between longitudinal axis and transverse axis measurements was 30 to 60 seconds. The end of a cycle was defined either by the observation of micturition or by the observation of dynamic changes in the bladder including reduction in lumen size and increase in wall thickness. The volume immediately before the end of the cycle was defined as the maximum bladder volume. Bladder volume was calculated from the three measured diameters by means of the formula for an ovoid sphere (4/3 'IT x Ll2 x T1I2 x T2/2 where L is the greatest longitudinal axis). For each study 15 to 20 such measurements were obtained. The corresponding time for each volume was the mean value of the time recorded at measurement of the longitudinal diameter and the time at measurement of the transverse diameters. For each fetus all volume measurements were plotted against time, and the hourly fetal urine production rate was calculated by regression analysis of all the bladder volumes during the filling phase of the first cycle (Fig. 1). In 42 patients a complete cycle was observed, and the time interval between the end of one cycle and the end of the next was recorded. Regression analysis (P. Royston's statistical package for personal computers, Tiberlake Clark Limited, London) was used to calculate the mean and individual 95%
Fetal urine production
Volume 161 Number 5
1265
•
_'20
~
...§.
.~
g
£
~..\ ~\ . \ ~Ii
\
'0
20
:
30
, 40
50
40
~
:s \
•
"
,
\
80
0
20 60
T'me(m'n)
Fig. 1. Fetal bladder volume measurements at 2- to 5-minute intervals. The slope of the filling phase, calculated by regression analysis, is used to estimate the hourly fetal urine production rate. If measurements are taken at 30-minute intervals, the slope of the apparent filling phase would be less and the hourly fetal urine production rate would be approximately half the actual value. confidence intervals of hourly fetal urine production rate and maximum bladder volume for gestational age. The data for hourly fetal urine production rate were normalized by log transformation before regression analysis was performed.
Results The hourly fetal urine production rate was calculated in all 85 patients; however, maximum bladder volumes were obtained for only 81 of the fetuses. Emptying of the fetal bladder was visualized on 101 occasions and in each case occurred in <30 seconds. In 28 cases emptying was complete, and in 55 cases the residual bladder volume was less than 25%; in 16 cases it was 26% to 50% of the maximum bladder volume. In two cases fetal micturition was observed and the residual volume was 60% and 65% of the maximum bladder volume, respectively. The hourly fetal urine production rate increases with advancing gestation from a mean value of 5 ml/hr at 20 weeks' gestation to 56 ml/hr at 41 weeks' gestation [Fig. 2; r = 0.853, n = 85,p < 0.0001, log 10 (hourly fetal urine production rate + 3) = 0.088 + 0.041 X weeks' gestation, SD = 0.169]. The maximum bladder volume increases with gestation from a mean value of 1 ml at 20 weeks' gestation to 36 ml at 41 weeks [r = 0.911, n = 81, P < 0.0001, log 10 (maximum bladder volume + 9) = 0.377 + 0.031 x weeks' gestation, SD = 0.094]. The mean time for the 42 complete cycles was 25 minutes (range, 7 to 43 minutes), and this did not change significantly with gestation (r = 0.191). In 24 cases there were two consecutive filling phases in which the hourly fetal urine production rate for each bladder filling was calculated. These were
25
30
Gestation
35
40
(wk)
Fig. 2. Reference range (mean and individual 95% confidence intervals) of the hourly fetal urine production rate.
compared by Student's paired t test (mean = 30.3 mllhr, SD = 25.8 and mean = 29.7 mllhr, SD = 25.7, respectively); there was no significant difference.
Comment The rate of fetal urine production increases with gestation, and the hourly fetal urine production rate is approximately double that reported in previous studies (Table I). ' -5 Furthermore, there is no apparent decrease of hourly fetal urine production rate near term as suggested by Wladimiroff and Campbell! The most likely reason for the disparity in results between this and previous studies is that the cycle length is shorter than the mean of 110 minutes reported by Campbell et al.' This point is illustrated in Fig. 1 in which calculation of the hourly fetal urine production rate from bladder volume measurements at 15- to 3D-minute intervals is half the value obtained from measurements taken every 2 to 5 minutes. The urine production rate of the fetus at term is considerably greater than that of the neonate (1 to 2 mllkg/hr). This may be because the insensible loss in the neonate is substantially greater than that of the fetus , which is surrounded by fluid. Furthermore, if unimpaired placental transfer is assumed, the fetus has a continuous supply of free water, whereas in the neonate the supply of fluid is restricted to feeding times. Real-time ultrasonography has also allowed observations of fetal micturition and dynamic changes in bladder volume. Although studies with static scanners had suggested that bladder emptying may either occur over a few seconds or as a stepwise process over a period of 30 minutes,' this study indicates that under real-time imaging the bladder empties quickly in all cases. Previous studies used the method of Campbell et al.' to estimate hourly fetal urine production rate and reported that (1) in normal pregnancies there may be a diurnal variation in HFUPR; (2) in pregnancies complicated by fetal growth retardation the hourly fetal
1266 Rabinowitz at al.
November 1989 Am J Obstet Gynecol
Table I. Comparison of mean hourly fetal urine production rate (ml) at given gestational ages from various studies Gestational age (wk) Study Campbell et al.I Wladimiroff and Campbe1l2 Van Otterlo et aJ.3 Kurjak et aI.' Deutinger et aI.' Present study
20
5
40
9
4 6 14
urine production rate is decreased, whereas in pregnancies with maternal diabetes mellitus it is unchanged; and in (3) pregnancies complicated by idiopathic polyhydramnios the hourly fetal urine production rate can be decreased by maternal administration of indomethacin. The validity of these findings requires reevaluation by means of the methodology described in this study. 1 9 0
REFERENCES 1. Campbell S, Wladimiroff jW, Dewhurst CJ. The antenatal measurement of fetal urine production. j Obstet Gynaecol Br Commonw 1973;80:680-6. 2. Wladimiroff jW, Campbell S. Fetal urine-production rates in normal and complicated pregnancy. Lancet 1974; 1: 151-4. 3. Van Otterlo LC, Wladimiroff jW, Wallenburg HCS. Relationship between fetal urine production and amniotic fluid volume in normal pregnancy and pregnancy complicated by diabetes. Br j Obstet Gynaecol 1977;84:205-9.
10 8 8 8 18
12 12 12 10 12 22
15 15 15 12 14 27
18 18 18 14 18 33
23 24 23 19 20 41
28 27 26 26 22 51
4. Kurjak A, Kirkinen P, Latin V, Ivankovic D. Ultrasonic assessment of fetal kidney function in normal and complicated pregnancies. AM j OBSTET GYNECOL 1981; 141: 266-70. 5. Deutinger j, Bartl W, Pfersmann C, Neumark j, Bernaschek G. Fetal kidney volume and urine production in cases of fetal growth retardation. j Perinat Med 1987;15:30715. 6. Wladimiroff jW, Van Otterlo LC, Wallenburg HCS, Drogendijk AC. A combined ultrasonic and biochemical study of fetal renal function in the term fetus. Eur j Obstet Gynecol Reprod Bioi 1976;6:103-8. 7. Wladimiroff jW, Barentsen R, Wallenburg HCS, Drogendijk AC. Fetal urine production in a case of diabetes associated with polyhydramnios. Obstet Gynecol 1975;46: 100-2. 8. Kirshon B, Cotton DB. Polyhydramnios associated with a ring chromosome and low maternal serum u-fetoprotein levels managed with indomethacin. AM j OBSTET GYNECOL 1988; 158: 1063-4. 9. Chamberlain PF, Manning FA, Morrison I, Lange IR. Circadian rhythm in bladder volumes in the term human fetus. Obstet Gynecol 1984;64:657-60.