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Uteroplacental blood flow in diabetic pregnancy: Measurements with indium 113m and a computer-linked gamma camera
Uteroplacental blood flow in diabetic pregnancy: Measurements with indium 113m and a computer-linked gamma camera L.
NYLUND
N.-O.
LUNELL
R.
LEWANDER
B.
PERSSON
B.
SARBY
With the technical assistance of S. THORNSTROM Huddinge
and Stockholm, Sweden
The uteroplacental blood flow index in the last trimester of pregnancy in 26 women with diabetes mellitus was compared to that in 41 healthy control subjects. After an intravenous injection of 1 mCi of indium 113m, the radiation over the placenta was recorded with a computer-linked gamma camera. From time-activity analysis of the isotope accumulation curve, a uteroplacental blood flow index could be calculated. In the diabetic pregnant women, the maternal-placental blood flow index was reduced 35% to 45% compared to that in healthy women. The blood flow index tended to be further impaired in those diabetic women who had higher blood glucose values. (AM. J. OBSTET. GYNECOL.
144~298,
1982.)
GREATEST proportion of the total resistance to maternal-placental blood flow is found in the predecidual parts of the uterine spiral arteries.’ There are several pathologic conditions that could affect these arteries and result in a reduced blood flow through the placenta. Isotope studies have shown that both in preeclampsia* and in intrauterine growth retardation3 the uteroplacental blood flow is decreased. In diabetes, structural changes in the trophoblasts of the placenta4 and narrowing of the lumen of the arterioles in the placental bed5 have been described. Absence of changes in the same type of vessels has also been reported.6 In THE
From the Departments of Obstetrics and Gynecology, Radiology, and Medical Physics, Huddinge Hospital, and the Department of Pediatrics, Hospital, Karolinska Institutet.
University St. G&an’s
Supported by grants from Alltinna BB :s Minnesfond, E+ressen’s Perinatul Research Fund, and First of May Flower Annual Campaign for Children’s Health. Received
for publica&m
Revised April
30, 1982.
Accepted May
27, 1982.
February
1, 1982.
Reprint requests: Dr. Nils-Olov LuneU, Department of Obstetrics and Gynecology, Huddinge University Hospital, S-141 86 Huddinge, Sweden.
299
view of the structural placental changes denoted, studies of the uteroplacental blood flow in diabetic pregnancy would be of great interest. The few available investigations have given conflicting results. Gitsch and Janisch,’ using g9mTc0,, reported a decreased uteroplacental blood flow in four diabetic women, but Janisch and Leodolter,* who studied time-activity curves after the intravenous injection of technetium 99m in 24 pregnant diabetic patients, found no significant reduction in this blood flow. Von Stolp and associates9 analyzed .different variables of the timeactivity curves after the intravenous injection of i13*In to 24 diabetic pregnant women and reported that disturbances in uteroplacental blood perfusion could be detected in all cases of severe diabetes. Kaar and associates’O measured uteroplacental blood flow by means of an intravenous xenon 113 method with use partly of gamma cameras and partly of a scintillation detector system. They found a moderate impairment of uteroplacental blood flow in five patients (White’s Class A), and there was a marked decrease in seven patients (White’s Classes B to E). The aim of the present study was to compare uteroplacental blood flow in normal and diabetic pregnancies by means of a method previously described.3 0002-9378/82/190298+05$00.50/O
@ 1982TheC.V.Mosby
Co.
Volume 144 Number 3
Table
Uteroplacental
I. Clinical
data on mothers
and their newborn
position
Left lateral
(Group
1)
Sufrine
Diabetic (Grout
i: (18-36) 1 (O-3)
17 24 (18-37) 0 (O-2)
pregnancy
299
37 (32-41) 39 (37-42) 3,070(2,700-4,350) 50 (47-55) 10 (5-10) 520 (380-750) 1
2)
Left lateral (Group
Pregnancy
3)
Supine
(group
4)
36 (28-39) 40 (37-42) 3,400 (2,720-3,900) 51 (47-54) 10 (6-10) 575 (525-825) 0
i:, (22-38) 0 (O-3) 4A, 3B, 2C, 2D, 1F 35 (32-39) 39 (36-41) 3,575 (2,650-4,800) 52 (47-56) 10 (8-10) 640 (460-890) 4
14 28 (23-39) 1 (O-6) 8A, 4B, lC, 1F 36 (34-39) 39 (37-42) 3,580(2,460-4,450) 51 (47-53) 10 (Q-10) 540 (430-1,000) 4
0
0
0
2
0
0
1
0
n
Maternal age (yr) Parity White’s Class of diabetes Gestational age at scintigraphy (wk) Gestational age at delivery (wk) Birth weight (pm) Birth length (cm) Apgar score at 5 min Placental weight (gm) Infants large for gestational age (above ninetieth percentile)? Infants small for gestational age (below tenth percentile)t Preeclampsia
flow in diabetic
infants*
Normal pregnancy Maternal
blood
*Values given as median and range. tFor gestational age and sex according to Swedish standard curves see Reference 16. Table
II. Uteroplacental
blood
flow indices
in normal
and diabetic
pregnancies*
Normal pregnancy Maternal
position
&se time (set) Maximum activity (counts/ 10 set) Blood flow index (proportional to ml/set)
Diabetic
Left lateral (GrmP 1)
Supine G-q 2)
Left lateral (Group 3)
g&20-84) 900 (420- 1,540) 20.6 (7.4-51.3)
17 67 (35-100) 880 (460-1,504) 13.9 (6.1-30.1)
A: (30-95) 800 (369- 1,620) 11.6 (4.3-40.0)
jn-egnuncy Supine (Group
4)
fit (50-110) 742 (264-875) 9.2 (4.1-16.7)
*Values given as median and range.
Material The study, which was approved by the local ethical committee, was made in 14 women with insulindependent diabetes and in 12 women with gestational diabetes. The diagnosis of gestational diabetes was based on a pathologic glucose tolerance test. Clinical data, including the number of women in the different White classes, are given in Table I. The pregnant diabetic patients were treated as described earlier.‘* During their stay in the hospital, blood glucose was measured daily at 0700, 1000, 1500, and 1900 hours. The control group consisted of 41 patients who, after delivery, were considered to have had normal pregnancies. In these cases, the blood flow determination was made on clinical grounds, such as suspicion of placenta previa or intrauterine growth retardation. Only women with ventrally positioned placentas were studied. Since maternal position has a marked effect on uteroplacental blood flow,* both the diabetic and the control subjects were studied in either the 30 degrees left lateral recumbent position or the supine position.
Methods After an intravenous bolus injection of 1 mCi of 113mIn chloride, the radiation emanating from the placenta was recorded above the patient with a computerlinked gamma camera (Intertechnique CINE 200, Cenera1 Electric Radicamera 60). Serial scintigrams with lo-second intervals were obtained during 240 seconds after injection and stored on magnetic disks for subsequent time-activity analysis. A light pen system was used to encircle the placental region on the computer screen. The time-activity curve for this region was then calculated by the computer (Fig. 1). The maximum activity value in this curve is proportional to the blood volume of the placenta. The ratio between the maximum activity and the rise time of the curve defined as the time from 5% to 95% of maximum activity is a relative measure of the uteroplacental blood flow. This quotient is a comparable quantity from one patient to another and is denoted as the “blood flow index.” The mathematical considerations have been given in greater detail by Lunell and associates.3 The values obtained were not normally distributed. Therefore, the nonparametric Mann-Whitney U test
300
Nylund
et al.
October Am. J. Obstet.
1, 1982 Gynecol.
III. Uteroplacental blood flow index in diabetic pregnancies with infants of normal weight for gestational age and large-for-gestational age infants* Table
Normal weight Subject
12.3 (4.3-27.0) n=8 10.6 (6.0-40.0) n=4 N.S.
U-ML.
Large for gestational age
Diabetes
Significance
9.7 (5.7-16.7) n=8 6.1 (4.1-16.5) n=4 N.S.
*Values given as median and range.
u 0
I 60 TIME
I
1
120 AFTER
8
180
INJECTION
240 (8)
1. Radiation recorded by the gamma camera in the placental region after intravenous injection of 1 mCi of 113mIn. Fig.
was used to test hypotheses. For the same reason, the results are presented as median values and ranges. Correlations were tested with Spearman’s rank correlation test.
Results The median and range values of rise time, maximum activity, and blood flow index are presented in Table II. No differences were found when groups 1 and 3 were compared in regard to maternal age, parity, gestational age at scintigraphy, gestational age at term, birth weight, fetal length, and Apgar score. The median placental weight was higher in group 3 (p < 0.05). The same calculations for groups 2 and 4 showed no differences. Neither-groups 1 and 2 nor groups 3 and 4 differed in these variables, with the exception of a slightly greater median placental weight in group 2 than in group 1 (p < 0.05). Comparison
between
patients
in
left
lateral
and
The influence of maternal position on relative uteroplacental blood flow can be seen in Table II when the control subjects studied in the left lateral position were compared to those in the supine position. In the latter women, the median rise time was prolonged from 50 to 67 seconds (p < O.Ol), and the blood flow index was reduced from 20.6 to 13.9 (p < 0.05), compared to the left lateral recumbent group. The maximum activities were equal in the two groups. Thus, the uteroplacental blood flow index was about 30% lower in the supine position. No statistically sigsupine
positions.
nificant differences were found between the diabetic groups studied in the left lateral and supine positions, probably because of the small number of patients in these groups. Comparison
between
control
and
diabetic
patients.
When the control group and the diabetic group studied in the left lateral position were compared, a prolonged rise time (p < 0.05) and a blood flow index that was 45% lower (p < 0.05) were observed in the diabetic group (Table II). Measurement in the supine position. Also in the supine position, a diminished maternal placental blood flow was found in the diabetic group. The maximum activity was lower (p < 0.05) and the blood flow index was reduced 35% (p < 0.01) in comparison with the control group. Even if the two women with intrauterine growth-retarded pregnancies were excluded from the supine diabetic group, the blood flow index of 9.2 in this group was still significantly lower than that in the normal group (13.9, p < 0.01). Thus, diabetes seems to be associated with a reduced maternal placental blood flow even in the absence of intrauterine growth retardation. Comparisons within the diabetic group. A comparison was made between diabetic women who had given birth to infants who were of normal weight for gestational age and those with infants who were large for gestational age (Table III). The median uteroplacental blood flow indices were lower, although not significantly so, in the women with infants who were large for gestational age. There were no significant differences between the median blood flow indices of 12.0 in White’s Class A and 11.6 in White’s Classes B to F measured in the left lateral position. Neither did the corresponding median blood flow indices of 8.1 and 10.0, respectively, in the supine group differ statistically. An attempt was made to determine whether the achieved degree of blood glucose control correlated Measurement
in the left lateral
position.
Volume Number
144 3
Uteroplacental
with the uteroplacental blood flow. There was no correlation between any mean blood glucose levels measured during a week in hospital in the first trimester and uteroplacental blood flow measured in the last trimester. Fasting blood glucose levels from the week preceding scintigraphy were statistically unrelated to the blood flow values. However, when women with a mean blood glucose level below 5.5 mM at 10 AM during this week were compared with those with a level above 5.5 mM, the blood flow index was significantly higher in the women with better blood glucose control who were in the group studied in the left lateral position (Table IV). Maternal ages, parities, and placental weights were equal. No similar correlation was found in patients studied in the supine position. Spearman’s rank correlation test showed a positive correlation between gestational age at scintigraphy and blood flow index (r = 0.59; p < 0.05) in the supine group. No such correlation was found in the left lateral recumbent group. Maternal age and parity showed no correlation to the blood flow indices. Comparisons within the control group. A correlation was found between gestational age at scintigraphy and blood flow index in the supine group (r = 0.67, p < 0.01). No such correlation was found in left lateral group 1.
Comment The study clearly demonstrated that uteroplacental blood flow is diminished in diabetic pregnancies. Our observation of a reduction between 35% and 45% in the blood flow index compared to that in normal women is of the utmost interest. A high fetal birth weight is often seen in diabetic pregnancies. This suggests that there is no direct relationship between uteroplacental blood flow and fetal birth weight in diabetes. In fact, in our study there was a nonsignificant tendency toward lower blood flow values among mothers with infants who were large for gestational age. The fetal hypertrophy in diabetes must then rather be explained on a metabolic basis. The reduction in the blood flow index in gestational diabetes did not differ statistically from the reduction in more severe diabetes. This finding is supported by the observation of Jones and Fox4 that the abnormalities in placentas from women with excellently controlled gestational diabetes
REFERENCES
1. Bruce, N. W., and Abdul-Karim, R. W.: Mechanisms controlling maternal placental circulation, Clin. Obstet. Gynecol.
17:135,
1974.
2. Lunell, N.-O., Nylund, L. E., Lewander,
R., and Sarby,
blood
flow in diabetic
pregnancy
301
Table IV. Uteroplacental blood flow indices in relationship to maternal blood glucose control during the week preceding scintigraphy* Mean <5.5
&se time (set) Maximum activity (counts/ 10 set) Blood flow index (proportional to mllsec) P
blood glwose ??a
at IO >5.5
AM
mM
1,152 (880- 1,620)
5 70 (65-85) 390 (369-720)
16.0 (12.1-27.0)
6.0 (4.3-11.1)
:O (55-95)
co.01
*Values given as median and range. were identical to those in placentas from women with long-standing, moderately controlled diabetes mellitus. Bjork and Persson12 recently described an increased density of the diabetic placenta caused by enlargement of the villi. This condition might affect the uteroplacental blood flow since the intervillous space would then be reduced. This concept is, in fact, supported by the present findings, since the median maximum activity values of the isotope curve, which is considered to reflect the volume of the intervillous space,3 was lower in the diabetic than in the control groups (Table II). Interestingly, our data show that the greatest reduction in maximum activity was observed in mothers with higher blood glucose values at 10 AM. We have previously showed that the 10 AM blood glucose value is a good reflection of the blood glucose variability during the day. I3 The present data suggest that impaired blood glucose control is associated with a diminished uteroplacental blood flow index. In our study, there was a tendency toward a lower blood flow index in patients with impaired blood glucose control. A maternal blood glucose concentration that changed from hypoglycemia to hyperglycemia would produce fetal hyperinsulinemia. Experimentally induced hyperinsulinemia in fetal lambs has been shown to be associated with a reduction in fetal arterial such hypoxemia could influoxygen. I4 Hypothetically, ence the blood flow in a manner similar to that observed in other hypoxic conditions.‘”
B.: Uteroplacental blood flow in pre-eclampsia. Measurements with indium-113m and a computer-linked gamma camera, Clin. Exp. Hypertens. B1:105, 1982. 3. Lunell, N.-O., Sarby, B., Lewander, R., and Nylund, L. E.: Comparison of uteroplacental blood flow in normal and
302
Nylund
et al.
October
Am. J. Obstrt.
4.
5.
6. 7.
8.
9.
10.
in intrauterine growth retarded pregnancy, Gynecol. Obstet. Invest. 10: 106, 1979. Jones, C. J. P., and Fox, H.: Placental changes in gestational diabetes. An ultrastructural study, Obstet. Gynecol. 48:274, 1976. Emmrich, P., Birke, R., and Giidel, R.: Beitrag zur Morphologie der mvometralen und dezidualen Arterien bei normalen Schwangerschaften, EPH-gestosen und miitterlichem Diabetes mellitus, Pathol. Microbial. 43:38, 1975. Pinkerton, J. H. M.: The placental bed arterioles in diabetes, Proc. R. Sot. Med. 56:1021, 1963. Gitsch, E., and Janisch, H.: Durchstromungsmessung der Plazenta mit Radioisotopen, Z. Geburtshilfe Perinatol. 174:169, 1971. Janisch, H., and Leodolter, S.: Ergebnisse der Plazentadurchstromungsmessung bei Risikoschwangerschaften, Z. Geburtshilfe Perinatol. 177:74, 1973. Von Stolp, W., Hiinermann, B., Mund-Hoym, S., and Hansmann, M.: Zur Uberwachung der Risikoschwangerschaft, Fortschr. Med. 92:427, 1974. Kaar, K., Jouppila, P., Kuikka J., Luotola, H., Toivanen,
11.
12.
13. 14.
15.
16.
1, 198? Gynecd.
J., and Rekonen, A.: Intervillous blood Bow in normal and complicated late pregnancy measured by means of an intravenous ‘33Xe method, Acta Obstet. Gynecol. Scand. 59:7, 1980. Persson, B., Gentz, J., and Lunell, N.-O.: Diabetes m pregnancy, in Scarpelli, E. M., and Cosmi, E. V., editors: Reviews in Perinatal Medicine, vol. 2, New York, 1978. Raven Press. BjGrk, O., and Persson, B.: Placental changes in relation to the degree of metabolic control in diabetes mellitus, Placenta. Yin press.) Persson. B.. and Lunell. N.-O.: Metabolic control in diabetic pregnancy, AM. J. &ST.ET. GYNECOL. 122:737, 1975. Philipps, A. F., Dubin, J. W., and Raye, J. R.: Fetal metabolic response to endogenous insulin release, AM. J. OBSTET. GYNECOL. 139:441,1981. Karlsson, K.: The influence of hypoxia on uterine and maternal placental blood flow, and the effect of alphaadrenergic blockade, J. Perinat. Med. 2:176, 1974. Sterky, G.: Swedish standard curves for intrauterine growth, Pediatrics 46:7. 1970.
NYLUND
N.-O.
LUNELL
R.
LEWANDER
B.
PERSSON
B.
SARBY
With the technical assistance of S. THORNSTROM Huddinge
and Stockholm, Sweden
The uteroplacental blood flow index in the last trimester of pregnancy in 26 women with diabetes mellitus was compared to that in 41 healthy control subjects. After an intravenous injection of 1 mCi of indium 113m, the radiation over the placenta was recorded with a computer-linked gamma camera. From time-activity analysis of the isotope accumulation curve, a uteroplacental blood flow index could be calculated. In the diabetic pregnant women, the maternal-placental blood flow index was reduced 35% to 45% compared to that in healthy women. The blood flow index tended to be further impaired in those diabetic women who had higher blood glucose values. (AM. J. OBSTET. GYNECOL.
144~298,
1982.)
GREATEST proportion of the total resistance to maternal-placental blood flow is found in the predecidual parts of the uterine spiral arteries.’ There are several pathologic conditions that could affect these arteries and result in a reduced blood flow through the placenta. Isotope studies have shown that both in preeclampsia* and in intrauterine growth retardation3 the uteroplacental blood flow is decreased. In diabetes, structural changes in the trophoblasts of the placenta4 and narrowing of the lumen of the arterioles in the placental bed5 have been described. Absence of changes in the same type of vessels has also been reported.6 In THE
From the Departments of Obstetrics and Gynecology, Radiology, and Medical Physics, Huddinge Hospital, and the Department of Pediatrics, Hospital, Karolinska Institutet.
University St. G&an’s
Supported by grants from Alltinna BB :s Minnesfond, E+ressen’s Perinatul Research Fund, and First of May Flower Annual Campaign for Children’s Health. Received
for publica&m
Revised April
30, 1982.
Accepted May
27, 1982.
February
1, 1982.
Reprint requests: Dr. Nils-Olov LuneU, Department of Obstetrics and Gynecology, Huddinge University Hospital, S-141 86 Huddinge, Sweden.
299
view of the structural placental changes denoted, studies of the uteroplacental blood flow in diabetic pregnancy would be of great interest. The few available investigations have given conflicting results. Gitsch and Janisch,’ using g9mTc0,, reported a decreased uteroplacental blood flow in four diabetic women, but Janisch and Leodolter,* who studied time-activity curves after the intravenous injection of technetium 99m in 24 pregnant diabetic patients, found no significant reduction in this blood flow. Von Stolp and associates9 analyzed .different variables of the timeactivity curves after the intravenous injection of i13*In to 24 diabetic pregnant women and reported that disturbances in uteroplacental blood perfusion could be detected in all cases of severe diabetes. Kaar and associates’O measured uteroplacental blood flow by means of an intravenous xenon 113 method with use partly of gamma cameras and partly of a scintillation detector system. They found a moderate impairment of uteroplacental blood flow in five patients (White’s Class A), and there was a marked decrease in seven patients (White’s Classes B to E). The aim of the present study was to compare uteroplacental blood flow in normal and diabetic pregnancies by means of a method previously described.3 0002-9378/82/190298+05$00.50/O
@ 1982TheC.V.Mosby
Co.
Volume 144 Number 3
Table
Uteroplacental
I. Clinical
data on mothers
and their newborn
position
Left lateral
(Group
1)
Sufrine
Diabetic (Grout
i: (18-36) 1 (O-3)
17 24 (18-37) 0 (O-2)
pregnancy
299
37 (32-41) 39 (37-42) 3,070(2,700-4,350) 50 (47-55) 10 (5-10) 520 (380-750) 1
2)
Left lateral (Group
Pregnancy
3)
Supine
(group
4)
36 (28-39) 40 (37-42) 3,400 (2,720-3,900) 51 (47-54) 10 (6-10) 575 (525-825) 0
i:, (22-38) 0 (O-3) 4A, 3B, 2C, 2D, 1F 35 (32-39) 39 (36-41) 3,575 (2,650-4,800) 52 (47-56) 10 (8-10) 640 (460-890) 4
14 28 (23-39) 1 (O-6) 8A, 4B, lC, 1F 36 (34-39) 39 (37-42) 3,580(2,460-4,450) 51 (47-53) 10 (Q-10) 540 (430-1,000) 4
0
0
0
2
0
0
1
0
n
Maternal age (yr) Parity White’s Class of diabetes Gestational age at scintigraphy (wk) Gestational age at delivery (wk) Birth weight (pm) Birth length (cm) Apgar score at 5 min Placental weight (gm) Infants large for gestational age (above ninetieth percentile)? Infants small for gestational age (below tenth percentile)t Preeclampsia
flow in diabetic
infants*
Normal pregnancy Maternal
blood
*Values given as median and range. tFor gestational age and sex according to Swedish standard curves see Reference 16. Table
II. Uteroplacental
blood
flow indices
in normal
and diabetic
pregnancies*
Normal pregnancy Maternal
position
&se time (set) Maximum activity (counts/ 10 set) Blood flow index (proportional to ml/set)
Diabetic
Left lateral (GrmP 1)
Supine G-q 2)
Left lateral (Group 3)
g&20-84) 900 (420- 1,540) 20.6 (7.4-51.3)
17 67 (35-100) 880 (460-1,504) 13.9 (6.1-30.1)
A: (30-95) 800 (369- 1,620) 11.6 (4.3-40.0)
jn-egnuncy Supine (Group
4)
fit (50-110) 742 (264-875) 9.2 (4.1-16.7)
*Values given as median and range.
Material The study, which was approved by the local ethical committee, was made in 14 women with insulindependent diabetes and in 12 women with gestational diabetes. The diagnosis of gestational diabetes was based on a pathologic glucose tolerance test. Clinical data, including the number of women in the different White classes, are given in Table I. The pregnant diabetic patients were treated as described earlier.‘* During their stay in the hospital, blood glucose was measured daily at 0700, 1000, 1500, and 1900 hours. The control group consisted of 41 patients who, after delivery, were considered to have had normal pregnancies. In these cases, the blood flow determination was made on clinical grounds, such as suspicion of placenta previa or intrauterine growth retardation. Only women with ventrally positioned placentas were studied. Since maternal position has a marked effect on uteroplacental blood flow,* both the diabetic and the control subjects were studied in either the 30 degrees left lateral recumbent position or the supine position.
Methods After an intravenous bolus injection of 1 mCi of 113mIn chloride, the radiation emanating from the placenta was recorded above the patient with a computerlinked gamma camera (Intertechnique CINE 200, Cenera1 Electric Radicamera 60). Serial scintigrams with lo-second intervals were obtained during 240 seconds after injection and stored on magnetic disks for subsequent time-activity analysis. A light pen system was used to encircle the placental region on the computer screen. The time-activity curve for this region was then calculated by the computer (Fig. 1). The maximum activity value in this curve is proportional to the blood volume of the placenta. The ratio between the maximum activity and the rise time of the curve defined as the time from 5% to 95% of maximum activity is a relative measure of the uteroplacental blood flow. This quotient is a comparable quantity from one patient to another and is denoted as the “blood flow index.” The mathematical considerations have been given in greater detail by Lunell and associates.3 The values obtained were not normally distributed. Therefore, the nonparametric Mann-Whitney U test
300
Nylund
et al.
October Am. J. Obstet.
1, 1982 Gynecol.
III. Uteroplacental blood flow index in diabetic pregnancies with infants of normal weight for gestational age and large-for-gestational age infants* Table
Normal weight Subject
12.3 (4.3-27.0) n=8 10.6 (6.0-40.0) n=4 N.S.
U-ML.
Large for gestational age
Diabetes
Significance
9.7 (5.7-16.7) n=8 6.1 (4.1-16.5) n=4 N.S.
*Values given as median and range.
u 0
I 60 TIME
I
1
120 AFTER
8
180
INJECTION
240 (8)
1. Radiation recorded by the gamma camera in the placental region after intravenous injection of 1 mCi of 113mIn. Fig.
was used to test hypotheses. For the same reason, the results are presented as median values and ranges. Correlations were tested with Spearman’s rank correlation test.
Results The median and range values of rise time, maximum activity, and blood flow index are presented in Table II. No differences were found when groups 1 and 3 were compared in regard to maternal age, parity, gestational age at scintigraphy, gestational age at term, birth weight, fetal length, and Apgar score. The median placental weight was higher in group 3 (p < 0.05). The same calculations for groups 2 and 4 showed no differences. Neither-groups 1 and 2 nor groups 3 and 4 differed in these variables, with the exception of a slightly greater median placental weight in group 2 than in group 1 (p < 0.05). Comparison
between
patients
in
left
lateral
and
The influence of maternal position on relative uteroplacental blood flow can be seen in Table II when the control subjects studied in the left lateral position were compared to those in the supine position. In the latter women, the median rise time was prolonged from 50 to 67 seconds (p < O.Ol), and the blood flow index was reduced from 20.6 to 13.9 (p < 0.05), compared to the left lateral recumbent group. The maximum activities were equal in the two groups. Thus, the uteroplacental blood flow index was about 30% lower in the supine position. No statistically sigsupine
positions.
nificant differences were found between the diabetic groups studied in the left lateral and supine positions, probably because of the small number of patients in these groups. Comparison
between
control
and
diabetic
patients.
When the control group and the diabetic group studied in the left lateral position were compared, a prolonged rise time (p < 0.05) and a blood flow index that was 45% lower (p < 0.05) were observed in the diabetic group (Table II). Measurement in the supine position. Also in the supine position, a diminished maternal placental blood flow was found in the diabetic group. The maximum activity was lower (p < 0.05) and the blood flow index was reduced 35% (p < 0.01) in comparison with the control group. Even if the two women with intrauterine growth-retarded pregnancies were excluded from the supine diabetic group, the blood flow index of 9.2 in this group was still significantly lower than that in the normal group (13.9, p < 0.01). Thus, diabetes seems to be associated with a reduced maternal placental blood flow even in the absence of intrauterine growth retardation. Comparisons within the diabetic group. A comparison was made between diabetic women who had given birth to infants who were of normal weight for gestational age and those with infants who were large for gestational age (Table III). The median uteroplacental blood flow indices were lower, although not significantly so, in the women with infants who were large for gestational age. There were no significant differences between the median blood flow indices of 12.0 in White’s Class A and 11.6 in White’s Classes B to F measured in the left lateral position. Neither did the corresponding median blood flow indices of 8.1 and 10.0, respectively, in the supine group differ statistically. An attempt was made to determine whether the achieved degree of blood glucose control correlated Measurement
in the left lateral
position.
Volume Number
144 3
Uteroplacental
with the uteroplacental blood flow. There was no correlation between any mean blood glucose levels measured during a week in hospital in the first trimester and uteroplacental blood flow measured in the last trimester. Fasting blood glucose levels from the week preceding scintigraphy were statistically unrelated to the blood flow values. However, when women with a mean blood glucose level below 5.5 mM at 10 AM during this week were compared with those with a level above 5.5 mM, the blood flow index was significantly higher in the women with better blood glucose control who were in the group studied in the left lateral position (Table IV). Maternal ages, parities, and placental weights were equal. No similar correlation was found in patients studied in the supine position. Spearman’s rank correlation test showed a positive correlation between gestational age at scintigraphy and blood flow index (r = 0.59; p < 0.05) in the supine group. No such correlation was found in the left lateral recumbent group. Maternal age and parity showed no correlation to the blood flow indices. Comparisons within the control group. A correlation was found between gestational age at scintigraphy and blood flow index in the supine group (r = 0.67, p < 0.01). No such correlation was found in left lateral group 1.
Comment The study clearly demonstrated that uteroplacental blood flow is diminished in diabetic pregnancies. Our observation of a reduction between 35% and 45% in the blood flow index compared to that in normal women is of the utmost interest. A high fetal birth weight is often seen in diabetic pregnancies. This suggests that there is no direct relationship between uteroplacental blood flow and fetal birth weight in diabetes. In fact, in our study there was a nonsignificant tendency toward lower blood flow values among mothers with infants who were large for gestational age. The fetal hypertrophy in diabetes must then rather be explained on a metabolic basis. The reduction in the blood flow index in gestational diabetes did not differ statistically from the reduction in more severe diabetes. This finding is supported by the observation of Jones and Fox4 that the abnormalities in placentas from women with excellently controlled gestational diabetes
REFERENCES
1. Bruce, N. W., and Abdul-Karim, R. W.: Mechanisms controlling maternal placental circulation, Clin. Obstet. Gynecol.
17:135,
1974.
2. Lunell, N.-O., Nylund, L. E., Lewander,
R., and Sarby,
blood
flow in diabetic
pregnancy
301
Table IV. Uteroplacental blood flow indices in relationship to maternal blood glucose control during the week preceding scintigraphy* Mean <5.5
&se time (set) Maximum activity (counts/ 10 set) Blood flow index (proportional to mllsec) P
blood glwose ??a
at IO >5.5
AM
mM
1,152 (880- 1,620)
5 70 (65-85) 390 (369-720)
16.0 (12.1-27.0)
6.0 (4.3-11.1)
:O (55-95)
co.01
*Values given as median and range. were identical to those in placentas from women with long-standing, moderately controlled diabetes mellitus. Bjork and Persson12 recently described an increased density of the diabetic placenta caused by enlargement of the villi. This condition might affect the uteroplacental blood flow since the intervillous space would then be reduced. This concept is, in fact, supported by the present findings, since the median maximum activity values of the isotope curve, which is considered to reflect the volume of the intervillous space,3 was lower in the diabetic than in the control groups (Table II). Interestingly, our data show that the greatest reduction in maximum activity was observed in mothers with higher blood glucose values at 10 AM. We have previously showed that the 10 AM blood glucose value is a good reflection of the blood glucose variability during the day. I3 The present data suggest that impaired blood glucose control is associated with a diminished uteroplacental blood flow index. In our study, there was a tendency toward a lower blood flow index in patients with impaired blood glucose control. A maternal blood glucose concentration that changed from hypoglycemia to hyperglycemia would produce fetal hyperinsulinemia. Experimentally induced hyperinsulinemia in fetal lambs has been shown to be associated with a reduction in fetal arterial such hypoxemia could influoxygen. I4 Hypothetically, ence the blood flow in a manner similar to that observed in other hypoxic conditions.‘”
B.: Uteroplacental blood flow in pre-eclampsia. Measurements with indium-113m and a computer-linked gamma camera, Clin. Exp. Hypertens. B1:105, 1982. 3. Lunell, N.-O., Sarby, B., Lewander, R., and Nylund, L. E.: Comparison of uteroplacental blood flow in normal and
302
Nylund
et al.
October
Am. J. Obstrt.
4.
5.
6. 7.
8.
9.
10.
in intrauterine growth retarded pregnancy, Gynecol. Obstet. Invest. 10: 106, 1979. Jones, C. J. P., and Fox, H.: Placental changes in gestational diabetes. An ultrastructural study, Obstet. Gynecol. 48:274, 1976. Emmrich, P., Birke, R., and Giidel, R.: Beitrag zur Morphologie der mvometralen und dezidualen Arterien bei normalen Schwangerschaften, EPH-gestosen und miitterlichem Diabetes mellitus, Pathol. Microbial. 43:38, 1975. Pinkerton, J. H. M.: The placental bed arterioles in diabetes, Proc. R. Sot. Med. 56:1021, 1963. Gitsch, E., and Janisch, H.: Durchstromungsmessung der Plazenta mit Radioisotopen, Z. Geburtshilfe Perinatol. 174:169, 1971. Janisch, H., and Leodolter, S.: Ergebnisse der Plazentadurchstromungsmessung bei Risikoschwangerschaften, Z. Geburtshilfe Perinatol. 177:74, 1973. Von Stolp, W., Hiinermann, B., Mund-Hoym, S., and Hansmann, M.: Zur Uberwachung der Risikoschwangerschaft, Fortschr. Med. 92:427, 1974. Kaar, K., Jouppila, P., Kuikka J., Luotola, H., Toivanen,
11.
12.
13. 14.
15.
16.
1, 198? Gynecd.
J., and Rekonen, A.: Intervillous blood Bow in normal and complicated late pregnancy measured by means of an intravenous ‘33Xe method, Acta Obstet. Gynecol. Scand. 59:7, 1980. Persson, B., Gentz, J., and Lunell, N.-O.: Diabetes m pregnancy, in Scarpelli, E. M., and Cosmi, E. V., editors: Reviews in Perinatal Medicine, vol. 2, New York, 1978. Raven Press. BjGrk, O., and Persson, B.: Placental changes in relation to the degree of metabolic control in diabetes mellitus, Placenta. Yin press.) Persson. B.. and Lunell. N.-O.: Metabolic control in diabetic pregnancy, AM. J. &ST.ET. GYNECOL. 122:737, 1975. Philipps, A. F., Dubin, J. W., and Raye, J. R.: Fetal metabolic response to endogenous insulin release, AM. J. OBSTET. GYNECOL. 139:441,1981. Karlsson, K.: The influence of hypoxia on uterine and maternal placental blood flow, and the effect of alphaadrenergic blockade, J. Perinat. Med. 2:176, 1974. Sterky, G.: Swedish standard curves for intrauterine growth, Pediatrics 46:7. 1970.