- Email: [email protected]
Relationship between maternal and fetal blood glucose during labor
Relationship
between maternal and fetal
blood glucose during labor PETER LYN CARL Melbourne,
PATERSON,
M.B.B.S.,
PHILLIPS,
DIP.
WOOD,
M.B.B.S.,
F.R.A.C.S.
A.I.M.L.T. F.R.C.S.,
M.R.C.O.G.
Australia
The metabolism of glucose is extremely important to both the fetus and neonate, but previous investigations into the relationships between maternal and fetal blood glucose concentrations have been restricted by the use of cord blood specimens. In the present study the technique of fetal blood collection through the partially dilated cervix has been employed. Blood glucose concentration in the fetus during labor was found to be closely related to the maternal concentration and was increased in the cord at delivery only in those cases in which the maternal level had also risen. Elevation of maternal and fetal blood glucose levels were produced by intravenous dextrose. With rapid injection comparable, elevations of maternal and fetal levels were produced and both had returned to preinjection levels after 2 hours. The lowest fetal blood glucose was found in association with seuere fetal hypoxia resulting from placental insuficiency. Even in this case, fetal blood glucose was rapidly elevated by a maternal dextrose infusion
T H E F E T A L and adult brains depend on glucose as an energy source. There is experimental and clinical evidence that the extent of the cerebral cortical damage produced by hypoxia during labor is partly related to the availability of glucose, which in turn is deadequate hepatic glycogen pendent on storesl, ’ Hypoglycemia may develop in the neonate who suffered from placental insufficiency in utero, and has been shown to be associated with depleted glycogen stores.‘, 3 The serious nature of the condition was shown by the fact that of 40 such babies, 5 died and 8 showed evidence of mental retardation later in life.3 In view of the extreme importance of carbohydrate metabolism to both fetus and neonate, the relationship between fetal and maternal blood glucose concentrations during labor was studied, and the possibility of
affecting infusions
these levels by maternal was investigated.
dextrose
Method
Measurement of blood glucose concentration. Capillary blood specimens were obtained from the scalp of the fetus during labor using the method described by Saling.4 Cord blood specimens were obtained by puncturing the appropriate vessel in an excised segment of cord while maternal and neonatal specimens were collected by finger and heel prick, respectively. The samples were placed in small tubes, mixed with sodium fluoride to prevent glycolysis, and the glucose concentration estimated by an ultramicro adaptation of the technique described by Kestor? and Teller.G The method entails the spectrocolorimetric comparison of the sample against a standard after the addition of glucose oxidase. Experimental
From the Department of Obstetrics and Gynecology, Monash University Medical School, Queen Victoria Hospital.
procedures
1. In 6 patients a fetal and maternal blood glucose estimation was performed dur-
938
Volume Number
98 7
Maternal
ing labor and at the time of delivery. The concentration in the neonate at 1 hour and 24 hours was also determined. 2. In 9 patients an infusion of 100 Gm. dextrose was given over 2 hours of their labor and maternal and fetal blood glucose were measured before and after the infusion. 3. In 6 patients 50 Gm. dextrose was injected intravenously in 5 minutes and maternal and fetal blood glucose levels were measured before, and at vz and 2 hours following the injection. Measurements were also performed on the cord blood at delivery and on the neonate 1 and 24 hours later. Results
Normal blood glucose concentrations in labor. A positive gradient in the concentrations of blood glucose, from mother to fetus, was demonstrated in each case. The mean maternal level was 102 mg. per cent (S. D. + 33; n = 21) and the mean fetal blood glucose during labor was 75 mg. per cent (S. D. + 15). As illustrated in Fig. 1, a positive correlation between maternal and fetal blood glucose levels was found, r = +0.573, p
Table I. Maternal, in 6 controls
fetal,
and neonatal
blood
Maternal Patient N. M.
Fl1C.l
glucose
concentrations
Fetal Umbilical artery
Labor 71 73 71 80 79 74
66 64 84 80 88 68
93
74 +4
?3a
96
llOOD
514
ouco*s
during
labor
939
aoa ~~~C~NIIAWJN
Fig. 1. Correlation between blood glucose concentrations
78 84 99 118 95 86
Mean D.
glucose
100
Delivery
75
blood
I
73 87 175 85 82
fetal
maternal blood glucose at birth in only one patient (Table I). The mean umbilical venous concentration was 3 mg. per cent higher than that of the umbilical artery, although this difference was not statistically significant. The mean concentration at 1 hour in the neonate was 10 mg. per cent lower than that in the umbilical vein (p
Labor
L. P. P. K. A. G. R. G. B. B. S.
and
maternal and fetal during labor.
(mg. %)
Neonatal
Umbilical vein
fmflll,
I Hour
24 Hour
68 68 88 88 a5 70
60 64 66 78 78 64
64 62 62 71 70 54
75
78
210
210
68 f7
64 +6
940
Paterson,
Phillips,
and
Wood
given in the presence of severe fetal asphyxia which led to its death. Placental insufficiency had been diagnosed by retardation of fetal growth and decreased urinary estriol excretion. During labor the fetal blood glucose was 38 mg. per cent with associated fetal acidosis (pH 7.13, pC0, 48 mm. Hg, standard bicarbonate 14 mEq./L.) . Eighteen grams of the alkali tris (hydroxymethyl) aminomethane (THAM) was infused with the dextrose as this raises fetal pH and standard bicarbonate levels when infused to mothers.7 After completion of the infusion the glucose concentration in the fetus had
trebled to 108 mg. per cent but despite the correction of an associated maternal acidosis the fetal pH decreased (pH 6.79, pCO, 79 mm. Hg, standard bicarbonate 7.6 mEq. ’ L.) (Fig. 2). The fetal heart monitor ceased recording some 20 minutes later and after a further 20 minutes the fetus was stillborn. Postmortem examination showed evidence of fetal hypoxia resulting from placental infarction. Rapid injection of 50 Gm. dextrose. The fetal blood glucose concentration increased within 30 minutes in each case following the rapid intravenous injection of 50 Gm. dex-
Table II. Effect glucose in labor
on maternal
of infusion
of 100 Gm. dextrose
Blood Duration pregnancy (weeks)
Patient P. T.
35
F. S. M. p.*
42 40
M. L. E. G. M. G. E. S. M. K. I. G.
42 31 39 40 39 36
of
had gestational
Table
III.
Patient A. J. A. T. M.
K. E. M. N. N.
E. S. Mean S. D.
glucose
concentration
(mg.
Maternal
Antenatal abnolmality Poor fetal growth rate with low urinary estriol excretion Nil Hydramnios and pre-eclampsia Nil Proteinuria Nil Hypertension Nil Pre-eclampsia
Mean S. D. *Patient
and fetal blood %)
Fetal
Before
After
Before
After
84
156
38
108
94 ?lO
167 360
81 9’
109 285
96 153 12; 76 104 91
280 275 168 192 283 215
87 108 88 58 73 84
124 265 168 139 168 1’0
115 i43
233 269
79 20
165 ‘65
diabetes.
Effect of rapid Duration of pregnancy (weeks) 40 40 39 41 38
injection
of 50 Gm. dextrose on maternal - -__--I----______--__ Before
Antenatal abnormality Nil Pre-eclampsia Nil Pre-eclampsia Hypertension pre-eclampsia Pre-eclampsia
and
37
.____~
and fetal
blood
glucose
in labox Blood
Mate! 1
v2 Hour
glucose
ua1 1
2 Ho~r-~~/~
Deli~e~ymp
90 77 101 100 79
265 232 200 240 “6-l
104 75 l(17 IO.1 78
99 97 IO6 83
89
300
X6
95
90 t 11
250 5 34
o:! + 11
i
96 2:
Volume Number
98 7
Maternal
18G.
Fig. and
concentrations
2. The capillary
THMl,
1006.
and
fetal
blood
during
labor
DELIVERY
DEXTROSE
effect of the infusion of 100 Gm. of dextrose blood glucose of mother (A) and fetus (0)
and 18 Gm. of THAM in a case of placental
on the pH insufficiency.
(mg.%) L%eonatal
Fetal Before
glucose
Deliuery
I Hour
66 43 64 83 74
1
$4 Hour 232 212 165 186 250
1
2 Hour 76 40 67 95 78
1
76 78 67 104 73
72 84 54 8-t 65
70 23 46 74 55
69
226
75
73
66
48
67 213
212 + 32
72 t18
79 13
71 *12
53 +18
t
24 Hour
941
942
Paterson,
Phillips,
and
.4ugust 1. I%7 ~\m. J. Obst. & Gym-.
Wood
trose (Table III). A close correlation existed between fetal and maternal levels (Fig. 3 i both trebling within 30 minutes and falling almost to preinjection levels after 2 hours. Labor was induced in Patient J. E. hrcause of severe pre-eclampsia with proteinuria. The fetal blood glucose concentration initially was 43 mg. per cent, rose to 212 mg. per cent half an hour after the intravenous injection, but fell to 40 mg. per cent at 2 hours. The cord blood level of 78 mg. per cent was in the normal range as was the acid base status. However, the neonatal blood glucose fell to 23 mg. per cent 24 hours after birth suggesting that the hepatic glycogen stores may have been depleted (Fig. 4).
Fig. 3. Mean maternal (A) and fetal (0) blood glucose concentrations following rapid injection of 50 Gm. of glucose to 6 mothers.
I
I
3
4 HOURS
BEFORE
The mean umbilical venous level and neonatal blood glucose of this group were similar to those of the mothers given no parenteral glucose during labor, and combined analysis of these 12 cases shows a statistically significant fall in blood glucose of the neonate in the first hour after birth
t 2 DELlVERY
1
4
12
0 HOURS
Fig. 4. Effect of injection of 50 Gm. of dextrose on maternal cose concentrations in a case of pre-eclampsia with proteinuria. 24 hour neonatal levels suggested depleted glycogen stores.
AFTER
16
20
DELIVERY
(A) The
and fetal (0) low base-line
blood fetal
gluand
Volumr Number
98 7
(p <0.05) with a further fall of 18 mg. per cent 24 hours later (p <0.02). Comment
In 1866, Claude Bernard observed an elevation of blood glucose levels following acute stress or injury. The elevation has been attributed to an increase in blood epinephrine concentrations* which activates the enzyme phosphorylase involved in the degradation of glycogen to glucose.g The absence of a significant elevation of blood glucose in 10 of the 12 mothers studied is consistent with the finding that plasma concentration or urinary excretion of catecholamines is either not raised during normal labor10l I1 or only increases slight1y.l’ The mean fetal blood glucose level during labor of 75 mg. per cent is in close agreement with that of Keele and associates13 who employed cord blood at delivery. It is lower than that of Stenger and associates14 but their specimens were obtained under anesthesia, which elevated the maternal blood glucose concentration. These authors also showed a tendency for the umbilical vein glucose level to be higher than in the umbilical artery which is in accord with our findings. Dawes and associates15 demonstrated a rise in blood glucose of lambs during acute asphyxia, and a similar increase has been observed in neonates with asphyxia at delivery by Takeda and associates1G which was attributed to increased plasma catecholamine and glucocorticoid levels. An elevation of fetal blood glucose at delivery relative to the concentration obtained during labor occurred in only 2 of our cases and in both the maternal level was also increased. No case, with clinical or biochemical evidence of acute asphyxia at delivery was studied. The lowest fetal blood sugar during labor (38 mg. per cent) was found in the patient (P. T.) in whom there was definite evidence of placental insufficiency and chronic asphyxia. A fetal blood concentration of only 43 mg. per cent was found in Patient J. E. in the presence of severe pre-eclampsia. Presumptive evidence of poor glycogen stores
Maternal
and
fetal
blood
glucose
during
labor
943
was afforded by the very low blood glucose in the neonate at 24 hours. A significant fall in the blood glucose during the 24 hours following delivery was demonstrated in our cases. This has been described by other authors who regarded concentrations as low as 20 to 30 mg. per cent as not uncommon in the first 48 hours. 3, I3 Shelley and Nelligar? found considerable depression of liver glycogen concentrations in babies who were “small for dates” and concluded from this and animal experiments that the blood glucose did not fall until the liver glycogen stores were almost completely exhausted. Cornblath and Reisner3 described a syndrome occurring in neonates born with evidence of placental insufficiency in which apnea or cyanotic attacks, convulsions, or feeding difficulties were found to be associated with blood glucose concentrations of less than 20 mg. per cent. They produced evidence that the syndrome was related to poor glycogen stores and drew attention to the seriousness of the condition if it was not recognized and treated. A close correlation between fetal and maternal blood glucose during labor with a concentration gradient from mother to fetus has been demonstrated. Similar results have been produced by Keele and associate?” using estimations confined to cord blood at delivery. Stenger and a.ssociates14 concluded that glucose was primarily in passive diffusion equilibrium between mother and fetus, under the influence of this gradient, but Folkhart, Dancis, and Money’? considered that the process involved a molecular sterospecific transport mechanism rather than simple diffusion, Ely I8 has produced further evidence in favor of an active transport mechanism. She perfused guinea pig placentas, which are morphologically similar to those of the human, and showed that the mechanisms could be saturated in the presence of very high maternal glucose levels. The possibility that an active mechanism dependent on oxygen is not present is suggested by the finding that glucose transfer continues under anoxic conditions1g and it is interesting that glucose transfer occurred
944
Paterson,
Phillips,
and
August I,1967 .4m. .I. Obst. & Gynec.
Wood
in Patient P. T. despite biochemical and pathologic evidence of severe hypoxia. The cord levels of blood glucose in the treated and nontreated groups are very similar and both demonstrated the fall in the neonatal period, which has been noted by Cornblath and Reisne? and by Keele and associates,‘” and, therefore, it is possible that the glucose load was of no benefit to the fetus although fetal hepatic glycogen stores may have been increased during the period of fetal hyperglycemia. It must also be emphasized that the dextrose load was relatively small and in most cases was stopped some hours before delivery. The ability to raise cord blood glucose levels by infusions continued up to the time of delivery has been demonstrated by Morris, Wood, and Archer,“O and Scott’l has produced histologic evidence that hepatic and cardiac glycogen stores can be increased by neonatal fructose infusions. In the newborn lamb and monkey, Dawes and associates’s, 22, 23 showed that when glucose was infused during asphyxia with sufficient alkali to check the fall in pH, survival time was prolonged and histologic evidence of damage to the basal nuclei of the brain was reduced. The effect could not be produced by the maintenance of pH alone. Application of these finding has been limited in the past by the difficulties in assessing fetal asphyxia. This can now be done more precisely using fetal heart monitoring and fetal blood estimation of pH, pCO,, and standard bicarbonate and it is possible to
REFERENCES
Shelley, H. J.: Brit. M. Bull. 17: 137, 1961. Shelley, H. J.. and Nelligan, G. A.: Brit. M. Bull. 22: 34. 1966. 3. Cornblath, M., and Reisner, S. H.: New England J. Med. 273: 378, 1965. 4. Saling, E. H.: Address given at Yale University School of Medicine, 1964. 5. Keston, A. S.: Abstracts of papers one hundred twenty-ninth meeting American College of Surgeons, 1956, p. 31C. J. D.: Abstracts of papers one hun6. Teller, dred thirtieth meeting American College of Surgeons, 1956, p. 69C. 7. Newman. W., Mitchell, P., and Wood, C.: AM. J. OBST. & GYNEC. 97: 52, 1967.
assess the effect on the fetus of maternal infusions of dextrose and THAM with subsequent fetal blood analyses. The use of parenteral dextrose infusions during labor in the presence of prematurity or placental insufficiency is justified. The ability to transfer some of the added glucose to the fetus in these situations has been demonstrated, and it may help to prevent or alleviate the hypoglycemia which is prone to occur in the neonatal period. It has been shown that this condition responds rapidly to dextrose infusions to the neonate with evidence of restoration of glycogen stores afforded by brisk response to glucagon.” We are grateful to the Honorary Obstetric~al Staff for allowing us access to their patients, and to the medical and technical staff of the Professorial Unit for their assistance with blood collections and their many helpful suggestions. WC also wish to thank the Felton Request who have supported this project financially. Addendum In 11 patients, maternal and fetal arid-base status was measured before and after an intravenous glucose load of 25 Gm. The fetal pH decreased by 0.06 (mean) over the next 2 hours \vhich sugge:sts that this dose of glucose is unlikely to prrvent feta1 acidosis. Twenty-five grams of glucose also was given to the mothers of 2 acidotic fetuses: in one the fetal pH increased from 7.16 to 7.24 and in the other the fetal pH decreased from 7.13 to 6.79. This experience of the effect of glue-osc therapy on fetal pH is different from that of Romney and Crabcl.z.*
8.
1. 2.
9. 10. 11. 12. 13. 14.
Pekkarinen, A.: The biochemical response to 1960. Blackwell Scientific iniurv. Oxford, P;bl&tions, p’217. ’ Sutherland. E. W.: Ann. New York Acad. Sc. 54: 693, 1$51. Gemzell, C. A., Robbe, H., and Strom, G.: Acta endocrinol. 23: 158. 1956. Stone, M. L., Piliero, S. J., Hammer, H., and Portnoy, A.: Obst. & Gynec. 16: 674, 1960. Beard, R., and Karem, S.: Personal communication. Keele. D. K., Kay, J. L., Brown, J., and Nordquist, B.: Pediatrics 37: 597, 1966. Stenger, V., Henry, J., Cestaric, E., Eitzman, D., and Prystowsky, H., AM. J. OBST. & GYNEC. 94: 261, 1966.
Volume
98
Number
7
15.
16. 17. 18. 19. 20.
Dawes, G. S., Jacobson, H. N., Mott, J. C., Shelley, H. J., and Stafford, A.: J. Physiol. 169: 167, 1963. Takeda, Y., et al.: J. Paediat. Prac. 28: 1277, 1965. Folkhart, G. R., Dancis, T., and Money, W. L.: AM. J. OBST. & GYNEC. 80: 221, 1960. Ely, P. A.: J. Physiol. 184: 255, 1966. Karvonen. M. T.. Laamen. A.. and Raiha. N.: Acta’ physiil.’ scandinab. 36: 245, 1956: Morris, E. D., Wood, C., and Archer, G.
Maternal
21. 22. 23. 24.
and
fetal
blood
glucose
during
labor
945
D.: J. Obst. & Gynaec. Brit. Comm. 71: 766, 1964. 40: 317, Scott, J. M.: Arch. Dis. Childhood 1965. Dawes, G. S., Mott, J. C., Shelley, H. J., and Stafford, A.: J. Physiol. 168: 43, 1963. Dawes, G. S., Hibbard, E., and Windle, W. F.: J. Pediat. 65: 801, 1964. Romney, S. L., and Gabel. P. V.: AM. J. OBST. & GYNEC. 95: 668. 1966.
between maternal and fetal
blood glucose during labor PETER LYN CARL Melbourne,
PATERSON,
M.B.B.S.,
PHILLIPS,
DIP.
WOOD,
M.B.B.S.,
F.R.A.C.S.
A.I.M.L.T. F.R.C.S.,
M.R.C.O.G.
Australia
The metabolism of glucose is extremely important to both the fetus and neonate, but previous investigations into the relationships between maternal and fetal blood glucose concentrations have been restricted by the use of cord blood specimens. In the present study the technique of fetal blood collection through the partially dilated cervix has been employed. Blood glucose concentration in the fetus during labor was found to be closely related to the maternal concentration and was increased in the cord at delivery only in those cases in which the maternal level had also risen. Elevation of maternal and fetal blood glucose levels were produced by intravenous dextrose. With rapid injection comparable, elevations of maternal and fetal levels were produced and both had returned to preinjection levels after 2 hours. The lowest fetal blood glucose was found in association with seuere fetal hypoxia resulting from placental insuficiency. Even in this case, fetal blood glucose was rapidly elevated by a maternal dextrose infusion
T H E F E T A L and adult brains depend on glucose as an energy source. There is experimental and clinical evidence that the extent of the cerebral cortical damage produced by hypoxia during labor is partly related to the availability of glucose, which in turn is deadequate hepatic glycogen pendent on storesl, ’ Hypoglycemia may develop in the neonate who suffered from placental insufficiency in utero, and has been shown to be associated with depleted glycogen stores.‘, 3 The serious nature of the condition was shown by the fact that of 40 such babies, 5 died and 8 showed evidence of mental retardation later in life.3 In view of the extreme importance of carbohydrate metabolism to both fetus and neonate, the relationship between fetal and maternal blood glucose concentrations during labor was studied, and the possibility of
affecting infusions
these levels by maternal was investigated.
dextrose
Method
Measurement of blood glucose concentration. Capillary blood specimens were obtained from the scalp of the fetus during labor using the method described by Saling.4 Cord blood specimens were obtained by puncturing the appropriate vessel in an excised segment of cord while maternal and neonatal specimens were collected by finger and heel prick, respectively. The samples were placed in small tubes, mixed with sodium fluoride to prevent glycolysis, and the glucose concentration estimated by an ultramicro adaptation of the technique described by Kestor? and Teller.G The method entails the spectrocolorimetric comparison of the sample against a standard after the addition of glucose oxidase. Experimental
From the Department of Obstetrics and Gynecology, Monash University Medical School, Queen Victoria Hospital.
procedures
1. In 6 patients a fetal and maternal blood glucose estimation was performed dur-
938
Volume Number
98 7
Maternal
ing labor and at the time of delivery. The concentration in the neonate at 1 hour and 24 hours was also determined. 2. In 9 patients an infusion of 100 Gm. dextrose was given over 2 hours of their labor and maternal and fetal blood glucose were measured before and after the infusion. 3. In 6 patients 50 Gm. dextrose was injected intravenously in 5 minutes and maternal and fetal blood glucose levels were measured before, and at vz and 2 hours following the injection. Measurements were also performed on the cord blood at delivery and on the neonate 1 and 24 hours later. Results
Normal blood glucose concentrations in labor. A positive gradient in the concentrations of blood glucose, from mother to fetus, was demonstrated in each case. The mean maternal level was 102 mg. per cent (S. D. + 33; n = 21) and the mean fetal blood glucose during labor was 75 mg. per cent (S. D. + 15). As illustrated in Fig. 1, a positive correlation between maternal and fetal blood glucose levels was found, r = +0.573, p
Table I. Maternal, in 6 controls
fetal,
and neonatal
blood
Maternal Patient N. M.
Fl1C.l
glucose
concentrations
Fetal Umbilical artery
Labor 71 73 71 80 79 74
66 64 84 80 88 68
93
74 +4
?3a
96
llOOD
514
ouco*s
during
labor
939
aoa ~~~C~NIIAWJN
Fig. 1. Correlation between blood glucose concentrations
78 84 99 118 95 86
Mean D.
glucose
100
Delivery
75
blood
I
73 87 175 85 82
fetal
maternal blood glucose at birth in only one patient (Table I). The mean umbilical venous concentration was 3 mg. per cent higher than that of the umbilical artery, although this difference was not statistically significant. The mean concentration at 1 hour in the neonate was 10 mg. per cent lower than that in the umbilical vein (p
Labor
L. P. P. K. A. G. R. G. B. B. S.
and
maternal and fetal during labor.
(mg. %)
Neonatal
Umbilical vein
fmflll,
I Hour
24 Hour
68 68 88 88 a5 70
60 64 66 78 78 64
64 62 62 71 70 54
75
78
210
210
68 f7
64 +6
940
Paterson,
Phillips,
and
Wood
given in the presence of severe fetal asphyxia which led to its death. Placental insufficiency had been diagnosed by retardation of fetal growth and decreased urinary estriol excretion. During labor the fetal blood glucose was 38 mg. per cent with associated fetal acidosis (pH 7.13, pC0, 48 mm. Hg, standard bicarbonate 14 mEq./L.) . Eighteen grams of the alkali tris (hydroxymethyl) aminomethane (THAM) was infused with the dextrose as this raises fetal pH and standard bicarbonate levels when infused to mothers.7 After completion of the infusion the glucose concentration in the fetus had
trebled to 108 mg. per cent but despite the correction of an associated maternal acidosis the fetal pH decreased (pH 6.79, pCO, 79 mm. Hg, standard bicarbonate 7.6 mEq. ’ L.) (Fig. 2). The fetal heart monitor ceased recording some 20 minutes later and after a further 20 minutes the fetus was stillborn. Postmortem examination showed evidence of fetal hypoxia resulting from placental infarction. Rapid injection of 50 Gm. dextrose. The fetal blood glucose concentration increased within 30 minutes in each case following the rapid intravenous injection of 50 Gm. dex-
Table II. Effect glucose in labor
on maternal
of infusion
of 100 Gm. dextrose
Blood Duration pregnancy (weeks)
Patient P. T.
35
F. S. M. p.*
42 40
M. L. E. G. M. G. E. S. M. K. I. G.
42 31 39 40 39 36
of
had gestational
Table
III.
Patient A. J. A. T. M.
K. E. M. N. N.
E. S. Mean S. D.
glucose
concentration
(mg.
Maternal
Antenatal abnolmality Poor fetal growth rate with low urinary estriol excretion Nil Hydramnios and pre-eclampsia Nil Proteinuria Nil Hypertension Nil Pre-eclampsia
Mean S. D. *Patient
and fetal blood %)
Fetal
Before
After
Before
After
84
156
38
108
94 ?lO
167 360
81 9’
109 285
96 153 12; 76 104 91
280 275 168 192 283 215
87 108 88 58 73 84
124 265 168 139 168 1’0
115 i43
233 269
79 20
165 ‘65
diabetes.
Effect of rapid Duration of pregnancy (weeks) 40 40 39 41 38
injection
of 50 Gm. dextrose on maternal - -__--I----______--__ Before
Antenatal abnormality Nil Pre-eclampsia Nil Pre-eclampsia Hypertension pre-eclampsia Pre-eclampsia
and
37
.____~
and fetal
blood
glucose
in labox Blood
Mate! 1
v2 Hour
glucose
ua1 1
2 Ho~r-~~/~
Deli~e~ymp
90 77 101 100 79
265 232 200 240 “6-l
104 75 l(17 IO.1 78
99 97 IO6 83
89
300
X6
95
90 t 11
250 5 34
o:! + 11
i
96 2:
Volume Number
98 7
Maternal
18G.
Fig. and
concentrations
2. The capillary
THMl,
1006.
and
fetal
blood
during
labor
DELIVERY
DEXTROSE
effect of the infusion of 100 Gm. of dextrose blood glucose of mother (A) and fetus (0)
and 18 Gm. of THAM in a case of placental
on the pH insufficiency.
(mg.%) L%eonatal
Fetal Before
glucose
Deliuery
I Hour
66 43 64 83 74
1
$4 Hour 232 212 165 186 250
1
2 Hour 76 40 67 95 78
1
76 78 67 104 73
72 84 54 8-t 65
70 23 46 74 55
69
226
75
73
66
48
67 213
212 + 32
72 t18
79 13
71 *12
53 +18
t
24 Hour
941
942
Paterson,
Phillips,
and
.4ugust 1. I%7 ~\m. J. Obst. & Gym-.
Wood
trose (Table III). A close correlation existed between fetal and maternal levels (Fig. 3 i both trebling within 30 minutes and falling almost to preinjection levels after 2 hours. Labor was induced in Patient J. E. hrcause of severe pre-eclampsia with proteinuria. The fetal blood glucose concentration initially was 43 mg. per cent, rose to 212 mg. per cent half an hour after the intravenous injection, but fell to 40 mg. per cent at 2 hours. The cord blood level of 78 mg. per cent was in the normal range as was the acid base status. However, the neonatal blood glucose fell to 23 mg. per cent 24 hours after birth suggesting that the hepatic glycogen stores may have been depleted (Fig. 4).
Fig. 3. Mean maternal (A) and fetal (0) blood glucose concentrations following rapid injection of 50 Gm. of glucose to 6 mothers.
I
I
3
4 HOURS
BEFORE
The mean umbilical venous level and neonatal blood glucose of this group were similar to those of the mothers given no parenteral glucose during labor, and combined analysis of these 12 cases shows a statistically significant fall in blood glucose of the neonate in the first hour after birth
t 2 DELlVERY
1
4
12
0 HOURS
Fig. 4. Effect of injection of 50 Gm. of dextrose on maternal cose concentrations in a case of pre-eclampsia with proteinuria. 24 hour neonatal levels suggested depleted glycogen stores.
AFTER
16
20
DELIVERY
(A) The
and fetal (0) low base-line
blood fetal
gluand
Volumr Number
98 7
(p <0.05) with a further fall of 18 mg. per cent 24 hours later (p <0.02). Comment
In 1866, Claude Bernard observed an elevation of blood glucose levels following acute stress or injury. The elevation has been attributed to an increase in blood epinephrine concentrations* which activates the enzyme phosphorylase involved in the degradation of glycogen to glucose.g The absence of a significant elevation of blood glucose in 10 of the 12 mothers studied is consistent with the finding that plasma concentration or urinary excretion of catecholamines is either not raised during normal labor10l I1 or only increases slight1y.l’ The mean fetal blood glucose level during labor of 75 mg. per cent is in close agreement with that of Keele and associates13 who employed cord blood at delivery. It is lower than that of Stenger and associates14 but their specimens were obtained under anesthesia, which elevated the maternal blood glucose concentration. These authors also showed a tendency for the umbilical vein glucose level to be higher than in the umbilical artery which is in accord with our findings. Dawes and associates15 demonstrated a rise in blood glucose of lambs during acute asphyxia, and a similar increase has been observed in neonates with asphyxia at delivery by Takeda and associates1G which was attributed to increased plasma catecholamine and glucocorticoid levels. An elevation of fetal blood glucose at delivery relative to the concentration obtained during labor occurred in only 2 of our cases and in both the maternal level was also increased. No case, with clinical or biochemical evidence of acute asphyxia at delivery was studied. The lowest fetal blood sugar during labor (38 mg. per cent) was found in the patient (P. T.) in whom there was definite evidence of placental insufficiency and chronic asphyxia. A fetal blood concentration of only 43 mg. per cent was found in Patient J. E. in the presence of severe pre-eclampsia. Presumptive evidence of poor glycogen stores
Maternal
and
fetal
blood
glucose
during
labor
943
was afforded by the very low blood glucose in the neonate at 24 hours. A significant fall in the blood glucose during the 24 hours following delivery was demonstrated in our cases. This has been described by other authors who regarded concentrations as low as 20 to 30 mg. per cent as not uncommon in the first 48 hours. 3, I3 Shelley and Nelligar? found considerable depression of liver glycogen concentrations in babies who were “small for dates” and concluded from this and animal experiments that the blood glucose did not fall until the liver glycogen stores were almost completely exhausted. Cornblath and Reisner3 described a syndrome occurring in neonates born with evidence of placental insufficiency in which apnea or cyanotic attacks, convulsions, or feeding difficulties were found to be associated with blood glucose concentrations of less than 20 mg. per cent. They produced evidence that the syndrome was related to poor glycogen stores and drew attention to the seriousness of the condition if it was not recognized and treated. A close correlation between fetal and maternal blood glucose during labor with a concentration gradient from mother to fetus has been demonstrated. Similar results have been produced by Keele and associate?” using estimations confined to cord blood at delivery. Stenger and a.ssociates14 concluded that glucose was primarily in passive diffusion equilibrium between mother and fetus, under the influence of this gradient, but Folkhart, Dancis, and Money’? considered that the process involved a molecular sterospecific transport mechanism rather than simple diffusion, Ely I8 has produced further evidence in favor of an active transport mechanism. She perfused guinea pig placentas, which are morphologically similar to those of the human, and showed that the mechanisms could be saturated in the presence of very high maternal glucose levels. The possibility that an active mechanism dependent on oxygen is not present is suggested by the finding that glucose transfer continues under anoxic conditions1g and it is interesting that glucose transfer occurred
944
Paterson,
Phillips,
and
August I,1967 .4m. .I. Obst. & Gynec.
Wood
in Patient P. T. despite biochemical and pathologic evidence of severe hypoxia. The cord levels of blood glucose in the treated and nontreated groups are very similar and both demonstrated the fall in the neonatal period, which has been noted by Cornblath and Reisne? and by Keele and associates,‘” and, therefore, it is possible that the glucose load was of no benefit to the fetus although fetal hepatic glycogen stores may have been increased during the period of fetal hyperglycemia. It must also be emphasized that the dextrose load was relatively small and in most cases was stopped some hours before delivery. The ability to raise cord blood glucose levels by infusions continued up to the time of delivery has been demonstrated by Morris, Wood, and Archer,“O and Scott’l has produced histologic evidence that hepatic and cardiac glycogen stores can be increased by neonatal fructose infusions. In the newborn lamb and monkey, Dawes and associates’s, 22, 23 showed that when glucose was infused during asphyxia with sufficient alkali to check the fall in pH, survival time was prolonged and histologic evidence of damage to the basal nuclei of the brain was reduced. The effect could not be produced by the maintenance of pH alone. Application of these finding has been limited in the past by the difficulties in assessing fetal asphyxia. This can now be done more precisely using fetal heart monitoring and fetal blood estimation of pH, pCO,, and standard bicarbonate and it is possible to
REFERENCES
Shelley, H. J.: Brit. M. Bull. 17: 137, 1961. Shelley, H. J.. and Nelligan, G. A.: Brit. M. Bull. 22: 34. 1966. 3. Cornblath, M., and Reisner, S. H.: New England J. Med. 273: 378, 1965. 4. Saling, E. H.: Address given at Yale University School of Medicine, 1964. 5. Keston, A. S.: Abstracts of papers one hundred twenty-ninth meeting American College of Surgeons, 1956, p. 31C. J. D.: Abstracts of papers one hun6. Teller, dred thirtieth meeting American College of Surgeons, 1956, p. 69C. 7. Newman. W., Mitchell, P., and Wood, C.: AM. J. OBST. & GYNEC. 97: 52, 1967.
assess the effect on the fetus of maternal infusions of dextrose and THAM with subsequent fetal blood analyses. The use of parenteral dextrose infusions during labor in the presence of prematurity or placental insufficiency is justified. The ability to transfer some of the added glucose to the fetus in these situations has been demonstrated, and it may help to prevent or alleviate the hypoglycemia which is prone to occur in the neonatal period. It has been shown that this condition responds rapidly to dextrose infusions to the neonate with evidence of restoration of glycogen stores afforded by brisk response to glucagon.” We are grateful to the Honorary Obstetric~al Staff for allowing us access to their patients, and to the medical and technical staff of the Professorial Unit for their assistance with blood collections and their many helpful suggestions. WC also wish to thank the Felton Request who have supported this project financially. Addendum In 11 patients, maternal and fetal arid-base status was measured before and after an intravenous glucose load of 25 Gm. The fetal pH decreased by 0.06 (mean) over the next 2 hours \vhich sugge:sts that this dose of glucose is unlikely to prrvent feta1 acidosis. Twenty-five grams of glucose also was given to the mothers of 2 acidotic fetuses: in one the fetal pH increased from 7.16 to 7.24 and in the other the fetal pH decreased from 7.13 to 6.79. This experience of the effect of glue-osc therapy on fetal pH is different from that of Romney and Crabcl.z.*
8.
1. 2.
9. 10. 11. 12. 13. 14.
Pekkarinen, A.: The biochemical response to 1960. Blackwell Scientific iniurv. Oxford, P;bl&tions, p’217. ’ Sutherland. E. W.: Ann. New York Acad. Sc. 54: 693, 1$51. Gemzell, C. A., Robbe, H., and Strom, G.: Acta endocrinol. 23: 158. 1956. Stone, M. L., Piliero, S. J., Hammer, H., and Portnoy, A.: Obst. & Gynec. 16: 674, 1960. Beard, R., and Karem, S.: Personal communication. Keele. D. K., Kay, J. L., Brown, J., and Nordquist, B.: Pediatrics 37: 597, 1966. Stenger, V., Henry, J., Cestaric, E., Eitzman, D., and Prystowsky, H., AM. J. OBST. & GYNEC. 94: 261, 1966.
Volume
98
Number
7
15.
16. 17. 18. 19. 20.
Dawes, G. S., Jacobson, H. N., Mott, J. C., Shelley, H. J., and Stafford, A.: J. Physiol. 169: 167, 1963. Takeda, Y., et al.: J. Paediat. Prac. 28: 1277, 1965. Folkhart, G. R., Dancis, T., and Money, W. L.: AM. J. OBST. & GYNEC. 80: 221, 1960. Ely, P. A.: J. Physiol. 184: 255, 1966. Karvonen. M. T.. Laamen. A.. and Raiha. N.: Acta’ physiil.’ scandinab. 36: 245, 1956: Morris, E. D., Wood, C., and Archer, G.
Maternal
21. 22. 23. 24.
and
fetal
blood
glucose
during
labor
945
D.: J. Obst. & Gynaec. Brit. Comm. 71: 766, 1964. 40: 317, Scott, J. M.: Arch. Dis. Childhood 1965. Dawes, G. S., Mott, J. C., Shelley, H. J., and Stafford, A.: J. Physiol. 168: 43, 1963. Dawes, G. S., Hibbard, E., and Windle, W. F.: J. Pediat. 65: 801, 1964. Romney, S. L., and Gabel. P. V.: AM. J. OBST. & GYNEC. 95: 668. 1966.