AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 7, NUMBER 2 April 1990
MAGNESIUM SULFATE AND INTRAPARTUM FETAL BEHAVIOR Boris M. Petrikovsky, M.D., Ph.D., and Anthony M. Vintzileos, M.D.
The effect of magnesium sulfate (MgSO4) in intrapartum fetal behavior as judged by heart rate cycl icity was investigated by comparing the fetal heart characteristics of 15 term fetuses whose mothers received MgSO4 with a control group of 54 healthy term fetuses whose mothers received noantepartum medications. The duration of different fetal heart cycles and percentage of time spent in a particular cycle except for cycle C (6 to 10 beats per minute) were not different between groups. Seventy-seven percent of fetuses of the study group versus 24% of fetuses in the control group exhibited markedly diminished variability (cycle A) and 8% versus 63%, respectively, experienced cycles of increased variability (cycle D). Our observations may explain the conflicting conclusions of previous reports regarding the affect of MgSO4 on fetal heart rate variability.
Magnesium sulfate (MgSO4) is a widely used medication for the treatment of preeclampsia and preterm labor. Its precise mechanism of action remains unknown, but it is believed to consist of inhibition of acetylcholine release at the motor end plate, thereby decreasing neuromuscular transmission. The maternal side effects of MgSO4, such as flushing, sense of warmth, nausea, depression of deep tendon reflexes, electrocardiographic changes, respiratory depression, hypothermia, are well documented. 12 The possible effects of MgSO4 on fetal heart rate (FHR) and behavior, however, have not been thoroughly investigated. Previous studies regarding the effect of MgSO4 on fetal heart variability have shown conflicting results. In one of the first studies, Babaknia and Niebyl3 reported a marked decrease in FHR variability in patients receiving MgSO4. In contrast, an increase in FHR variability after administration of MgSO4 was described by several other investigators.4*5 Finally, Stallworth et al6 and Canez et al7 failed to find any changes in FHR variability when MgSO4 was used. FHR variability, however, is dependent on intrauterine behavioral states, a concept that was not taken into consideration in the previous studies. The changes in intrauterine behavioral states are accompanied by FHR pattern changes,8 a phenomenon that has been previously denned by our group as fetal heart cyclicity.9 Our previous studies have dem-
onstrated that the presence of FHR cyclicity is compatible with fetal well-being.910 During the intrapartum period, the normal length and frequency of the different FHR cycles have been established for healthy term 10 and preterm11 fetuses. The purpose of the present study was to determine the effects of MgSO4 on intrapartum fetal behavior as judged by heart rate cyclicity. MATERIALS AND METHODS
This retrospective study included analysis of intrapartum FHR patterns from 15 term fetuses whose mothers received MgSO4 to prevent eclampsia. All patients were transported to the University of Connecticut Health Center from regional hospitals where they received a loading dose of MgSO4 (4 gm of 20% MgSO4 solution intravenously over a 20minute period) and were kept on a maintenance dose of 2 gm/hour. Serum MgSO4 levels were checked every 4 hours and were within therapeutic range (4.8 to 8.4 mg/dl) in all patients. All 15 cases had normal pregnancy outcome, as denned by the absence of congenital anomalies, intrauterine growth retardation, or signs of fetal distress on electronic FHR monitoring (such as severe variable decelerations, late decelerations). All neonates were born in satisfactory condition with 1- and
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, Connecticut Reprint requests: Dr. Petrikovsky, Department of Obstetrics and Gynecology, Maternal-Fetal Medicine, School of Medicine, State University of New York, Stony Brook, NY 11794-8091
154
Copyright © 1990 by Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
Downloaded by: University of British Columbia. Copyrighted material.
ABSTRACT
EFFECT OF MAGNESIUM SULFATE O N INTRAPARTUM FETUS/Petrikovsky, Vintzileos
RESULTS
A total of 15 patients were included in the study group. The mean gestational age was 37.2 weeks. The total duration of analyzed FHR tracing was 7284 minutes. The control group included 54 term patients. The mean gestational age was 38.4 weeks. The total duration of analyzed FHR tracing in the control group was 10,567 minutes. Cyclicity was observed in all fetuses in both groups. The characteristics of FHR cyclicity patterns in the study and control groups are shown in Table 1. As can be seen, all defined patterns of cyclicity, namely, cycles A, B, C, and D, were registered in both groups of fetuses. The durations of the individual FHR cycles, except for cycle C, were not different between the two groups. Cycles C were significantly shorter in the fetuses of the study group. The percentage of time spent by a fetus in a particular cycle, except for cycle C, was also not significantly different between the two groups; fetuses of the study group spent less time in cycle C. There were highly significant differences (p < 0.001) between the study and control groups in percentage of fetuses who experienced a given cycle at least once during labor. Seventy-seven percent of fetuses whose mothers received MgSO4 versus 24% of fetuses in
Table 1. Characteristics of FHR Cyclicity of Study and Control Groups (Mean ± SD) Control Group
Duration A B C D
of cycles (min) 41.69 ± 32.25 79.79 ±61.44 92.98 ± 74.03 41.18 ±36.26
Study Group
50.07 61.83 56.84 36.00
p Value*
± 33.14 ± 42.42 ± 40.99 ±0
NS NS p < 0.01 NS
Percent of total labor time spent in cycle A 19.72 ± 12.83 23.25 ± 15.93 B 37.81 ± 18.04 47.36 ±15.28 C 48.94 ± 18.90 34.47 ± 23.14 D 23.40 ± 20.38 3.76 ± 0
NS NS p < 0.05 NS
Percent of cases with some time in cycle A 24% 77% B 89% 100% C 94% 100% D 63% 8%
p < 0.001 NS NS p < 0.001
Percent of cases with change to next cycle in order 81.3% 93.9% — *NS: not significant.
the control group exhibited cycle A, and 8% versus 63%, respectively, experienced cycle D. DISCUSSION
FHR patterns together with other biophysical characteristics (such as fetal eye movements, fetal respirations, body movements) indicate a particular cycle of fetal behavior. Thus, cycle A with markedly diminished beat-to-beat variability corresponds to quiet sleep (non-REM) state and is usually associated with regular respirations and rare gross body movements. Cycle B is usually exhibited by a fetus in active (REM) sleep and is accompanied by irregular respirations and small body movements. Cycles C and D are seen in awake states (quiet and active, respectively).8 In our previous studies we established normative data regarding the frequency and length of intrapartum FHR cycles for healhty term 10 and noncompromised preterm fetuses.l x In the present study we compared the cyclic patterns of fetuses whose mothers received MgSO4 with those from healthy term fetuses. The duration of a particular cycle, which reflects the time spent by a fetus in a certain state, and the proportion of total labor time spent in an individual cycle were similar in both groups except for cycle C. There were significant differences in the duration and percentage of total labor time spent in cycle C and percentage of fetuses who experienced cycles A and D at least once. Seventy-seven percent of fetuses in the study group versus 24% in the control group exhibited diminished variability at some point during labor (cycle A). The fact that all the neonates in the study group were born in satisfactory condition (1- and 5-minute Apgar score above 7 and normal acid-base status of the umbilical cord blood) indicates that the diminished variability was a 155
Downloaded by: University of British Columbia. Copyrighted material.
5-minute Apgar scores of 7 or more and umbilical cord pH values more than 7.25. All analyzed FHR tracings were obtained by internal monitoring by means of a Litton monitor (models FM 750 or FM 660) with the patient in a supine or (right or left) lateral position. FHR cyclicity was defined as the ability of the fetus to exhibit different patterns of long-term variability in terms of amplitude range. The long-term variability was evaluated only between uterine contractions. The following cycles were identified according to the differences in long-term variability, which were determined with a transparency superimposed on the FHR tracing: Cycle A: 0 to 2.5 beats per minute (bpm); cycle B: 3 to 5 bpm; cycle C: 6 to 10 bpm; and cycle D: 11 to 20 bpm. Each cycle had to persist for a minimum of 3 minutes without interruptions and transition from one cycle to another had to be completed within a maximum of 3 minutes. The analysis of each FHR tracing was started with the first clearly identifiable transition rather than the first cycle because the length of the latter is unknown. The intrapartum characteristics of the FHR cyclicity in these 15 term fetuses on MgSO4 were compared with those of a control group of healthy term fetuses from uncomplicated pregnancies with normal pregnancy outcome. The characteristics of the FHR cyclicity of the normal control group has been previously reported by us. 10 The statistical analysis was performed by using Student's t test for continuous variables and chisquare or Fisher's exact test when appropriate (for categorical variables). Values less than 0.05 were considered as statistically significant.
reflection of a certain behavioral state rather than fetal hypoxia. The administration of MgSO4 to the mother neither affected the fetal capability to manifest all four described behavioral states nor changed their duration, except for cycle C. It did, though, increase the observed frequency of cycle A (which corresponds to quiet sleep) and decreased the incidence of cycle D (which corresponds to active awake).
156
3. 4.
5.
CONCLUSION
6.
Our observations may indeed explain the conflicting reports regarding the effect of MgSO4 on the FHR variability, since all patterns of variability could be seen; however, fetuses whose mothers are receiving MgSO4 experience more frequently cycles of diminished variability and less frequently cycles of increased variability.
7. 8.
9.
REFERENCES
10.
Wacker WEC, Pavis AF. Magnesium metabolism. N Engl J Med 278:65, 1968 2. Rodis JF, Deaton JL, Campbell WA, et al: Maternal hypo-
11.
April 1990
thermia: An unusual complication of magnesium sulfate therapy. Am J Obstet Gynecol 156:435, 1987 Babaknia A, Niebyl JR: The effect of magnesium sulfate on fetal heart rate baseline variability. Obstet Gynecol 51: 25, 1978 Hutchinson HT, Nichols MM, Kuhr CR, Vasicka A: Effects of magnesium sulfate on uterine contractility, intrauterine fetus and infant. Am J Obstet Gynecol 88:747, 1964 Petrie RH, Yeh SY, Murata Y, et al: The effects of drugs on fetal heart rate variability. Am J Obstet Gynecol 130:294, 1978 Stallworth JC, Sze-Ya Y, Petrie RH: The effect of magnesium sulfate on fetal heart rate variability and uterine activity. Am J Obstet Gynecol 140:702, 1981 Canez MS, Reed KL, Shenker L: Effect on maternal magnesium sulfate treatment on fetal heart rate variability. Am J Perinatol 2:167, 1987 van Vliet MAT, Martin CB, Nijhuis JC, Prechtl HFR: The relationship between fetal activity and behavioral states and fetal breathing movements in normal and growthretarded fetuses. Am J Obstet Gynecol 153:582, 1985 Vintzileos AM, Campbell WA, Bors-Koefoed R, et al: The relationship between cyclic variation of fetal heart rate patterns and cord pH in preterm gestations. Am J Perinatol. In press Petrikovsky BM, Vintzileos AM, Nochimson DJ: Heart rate cyclicity during labor in healthy term fetuses. Am J Perinatol. In press Petrikovsky BM, Vintzileos AM, Lerer T, Campbell WA: Heart rate cyclicity in preterm fetuses. In press
Downloaded by: University of British Columbia. Copyrighted material.
AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 7, NUMBER 2
MAGNESIUM SULFATE AND INTRAPARTUM FETAL BEHAVIOR Boris M. Petrikovsky, M.D., Ph.D., and Anthony M. Vintzileos, M.D.
The effect of magnesium sulfate (MgSO4) in intrapartum fetal behavior as judged by heart rate cycl icity was investigated by comparing the fetal heart characteristics of 15 term fetuses whose mothers received MgSO4 with a control group of 54 healthy term fetuses whose mothers received noantepartum medications. The duration of different fetal heart cycles and percentage of time spent in a particular cycle except for cycle C (6 to 10 beats per minute) were not different between groups. Seventy-seven percent of fetuses of the study group versus 24% of fetuses in the control group exhibited markedly diminished variability (cycle A) and 8% versus 63%, respectively, experienced cycles of increased variability (cycle D). Our observations may explain the conflicting conclusions of previous reports regarding the affect of MgSO4 on fetal heart rate variability.
Magnesium sulfate (MgSO4) is a widely used medication for the treatment of preeclampsia and preterm labor. Its precise mechanism of action remains unknown, but it is believed to consist of inhibition of acetylcholine release at the motor end plate, thereby decreasing neuromuscular transmission. The maternal side effects of MgSO4, such as flushing, sense of warmth, nausea, depression of deep tendon reflexes, electrocardiographic changes, respiratory depression, hypothermia, are well documented. 12 The possible effects of MgSO4 on fetal heart rate (FHR) and behavior, however, have not been thoroughly investigated. Previous studies regarding the effect of MgSO4 on fetal heart variability have shown conflicting results. In one of the first studies, Babaknia and Niebyl3 reported a marked decrease in FHR variability in patients receiving MgSO4. In contrast, an increase in FHR variability after administration of MgSO4 was described by several other investigators.4*5 Finally, Stallworth et al6 and Canez et al7 failed to find any changes in FHR variability when MgSO4 was used. FHR variability, however, is dependent on intrauterine behavioral states, a concept that was not taken into consideration in the previous studies. The changes in intrauterine behavioral states are accompanied by FHR pattern changes,8 a phenomenon that has been previously denned by our group as fetal heart cyclicity.9 Our previous studies have dem-
onstrated that the presence of FHR cyclicity is compatible with fetal well-being.910 During the intrapartum period, the normal length and frequency of the different FHR cycles have been established for healthy term 10 and preterm11 fetuses. The purpose of the present study was to determine the effects of MgSO4 on intrapartum fetal behavior as judged by heart rate cyclicity. MATERIALS AND METHODS
This retrospective study included analysis of intrapartum FHR patterns from 15 term fetuses whose mothers received MgSO4 to prevent eclampsia. All patients were transported to the University of Connecticut Health Center from regional hospitals where they received a loading dose of MgSO4 (4 gm of 20% MgSO4 solution intravenously over a 20minute period) and were kept on a maintenance dose of 2 gm/hour. Serum MgSO4 levels were checked every 4 hours and were within therapeutic range (4.8 to 8.4 mg/dl) in all patients. All 15 cases had normal pregnancy outcome, as denned by the absence of congenital anomalies, intrauterine growth retardation, or signs of fetal distress on electronic FHR monitoring (such as severe variable decelerations, late decelerations). All neonates were born in satisfactory condition with 1- and
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, Connecticut Reprint requests: Dr. Petrikovsky, Department of Obstetrics and Gynecology, Maternal-Fetal Medicine, School of Medicine, State University of New York, Stony Brook, NY 11794-8091
154
Copyright © 1990 by Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
Downloaded by: University of British Columbia. Copyrighted material.
ABSTRACT
EFFECT OF MAGNESIUM SULFATE O N INTRAPARTUM FETUS/Petrikovsky, Vintzileos
RESULTS
A total of 15 patients were included in the study group. The mean gestational age was 37.2 weeks. The total duration of analyzed FHR tracing was 7284 minutes. The control group included 54 term patients. The mean gestational age was 38.4 weeks. The total duration of analyzed FHR tracing in the control group was 10,567 minutes. Cyclicity was observed in all fetuses in both groups. The characteristics of FHR cyclicity patterns in the study and control groups are shown in Table 1. As can be seen, all defined patterns of cyclicity, namely, cycles A, B, C, and D, were registered in both groups of fetuses. The durations of the individual FHR cycles, except for cycle C, were not different between the two groups. Cycles C were significantly shorter in the fetuses of the study group. The percentage of time spent by a fetus in a particular cycle, except for cycle C, was also not significantly different between the two groups; fetuses of the study group spent less time in cycle C. There were highly significant differences (p < 0.001) between the study and control groups in percentage of fetuses who experienced a given cycle at least once during labor. Seventy-seven percent of fetuses whose mothers received MgSO4 versus 24% of fetuses in
Table 1. Characteristics of FHR Cyclicity of Study and Control Groups (Mean ± SD) Control Group
Duration A B C D
of cycles (min) 41.69 ± 32.25 79.79 ±61.44 92.98 ± 74.03 41.18 ±36.26
Study Group
50.07 61.83 56.84 36.00
p Value*
± 33.14 ± 42.42 ± 40.99 ±0
NS NS p < 0.01 NS
Percent of total labor time spent in cycle A 19.72 ± 12.83 23.25 ± 15.93 B 37.81 ± 18.04 47.36 ±15.28 C 48.94 ± 18.90 34.47 ± 23.14 D 23.40 ± 20.38 3.76 ± 0
NS NS p < 0.05 NS
Percent of cases with some time in cycle A 24% 77% B 89% 100% C 94% 100% D 63% 8%
p < 0.001 NS NS p < 0.001
Percent of cases with change to next cycle in order 81.3% 93.9% — *NS: not significant.
the control group exhibited cycle A, and 8% versus 63%, respectively, experienced cycle D. DISCUSSION
FHR patterns together with other biophysical characteristics (such as fetal eye movements, fetal respirations, body movements) indicate a particular cycle of fetal behavior. Thus, cycle A with markedly diminished beat-to-beat variability corresponds to quiet sleep (non-REM) state and is usually associated with regular respirations and rare gross body movements. Cycle B is usually exhibited by a fetus in active (REM) sleep and is accompanied by irregular respirations and small body movements. Cycles C and D are seen in awake states (quiet and active, respectively).8 In our previous studies we established normative data regarding the frequency and length of intrapartum FHR cycles for healhty term 10 and noncompromised preterm fetuses.l x In the present study we compared the cyclic patterns of fetuses whose mothers received MgSO4 with those from healthy term fetuses. The duration of a particular cycle, which reflects the time spent by a fetus in a certain state, and the proportion of total labor time spent in an individual cycle were similar in both groups except for cycle C. There were significant differences in the duration and percentage of total labor time spent in cycle C and percentage of fetuses who experienced cycles A and D at least once. Seventy-seven percent of fetuses in the study group versus 24% in the control group exhibited diminished variability at some point during labor (cycle A). The fact that all the neonates in the study group were born in satisfactory condition (1- and 5-minute Apgar score above 7 and normal acid-base status of the umbilical cord blood) indicates that the diminished variability was a 155
Downloaded by: University of British Columbia. Copyrighted material.
5-minute Apgar scores of 7 or more and umbilical cord pH values more than 7.25. All analyzed FHR tracings were obtained by internal monitoring by means of a Litton monitor (models FM 750 or FM 660) with the patient in a supine or (right or left) lateral position. FHR cyclicity was defined as the ability of the fetus to exhibit different patterns of long-term variability in terms of amplitude range. The long-term variability was evaluated only between uterine contractions. The following cycles were identified according to the differences in long-term variability, which were determined with a transparency superimposed on the FHR tracing: Cycle A: 0 to 2.5 beats per minute (bpm); cycle B: 3 to 5 bpm; cycle C: 6 to 10 bpm; and cycle D: 11 to 20 bpm. Each cycle had to persist for a minimum of 3 minutes without interruptions and transition from one cycle to another had to be completed within a maximum of 3 minutes. The analysis of each FHR tracing was started with the first clearly identifiable transition rather than the first cycle because the length of the latter is unknown. The intrapartum characteristics of the FHR cyclicity in these 15 term fetuses on MgSO4 were compared with those of a control group of healthy term fetuses from uncomplicated pregnancies with normal pregnancy outcome. The characteristics of the FHR cyclicity of the normal control group has been previously reported by us. 10 The statistical analysis was performed by using Student's t test for continuous variables and chisquare or Fisher's exact test when appropriate (for categorical variables). Values less than 0.05 were considered as statistically significant.
reflection of a certain behavioral state rather than fetal hypoxia. The administration of MgSO4 to the mother neither affected the fetal capability to manifest all four described behavioral states nor changed their duration, except for cycle C. It did, though, increase the observed frequency of cycle A (which corresponds to quiet sleep) and decreased the incidence of cycle D (which corresponds to active awake).
156
3. 4.
5.
CONCLUSION
6.
Our observations may indeed explain the conflicting reports regarding the effect of MgSO4 on the FHR variability, since all patterns of variability could be seen; however, fetuses whose mothers are receiving MgSO4 experience more frequently cycles of diminished variability and less frequently cycles of increased variability.
7. 8.
9.
REFERENCES
10.
Wacker WEC, Pavis AF. Magnesium metabolism. N Engl J Med 278:65, 1968 2. Rodis JF, Deaton JL, Campbell WA, et al: Maternal hypo-
11.
April 1990
thermia: An unusual complication of magnesium sulfate therapy. Am J Obstet Gynecol 156:435, 1987 Babaknia A, Niebyl JR: The effect of magnesium sulfate on fetal heart rate baseline variability. Obstet Gynecol 51: 25, 1978 Hutchinson HT, Nichols MM, Kuhr CR, Vasicka A: Effects of magnesium sulfate on uterine contractility, intrauterine fetus and infant. Am J Obstet Gynecol 88:747, 1964 Petrie RH, Yeh SY, Murata Y, et al: The effects of drugs on fetal heart rate variability. Am J Obstet Gynecol 130:294, 1978 Stallworth JC, Sze-Ya Y, Petrie RH: The effect of magnesium sulfate on fetal heart rate variability and uterine activity. Am J Obstet Gynecol 140:702, 1981 Canez MS, Reed KL, Shenker L: Effect on maternal magnesium sulfate treatment on fetal heart rate variability. Am J Perinatol 2:167, 1987 van Vliet MAT, Martin CB, Nijhuis JC, Prechtl HFR: The relationship between fetal activity and behavioral states and fetal breathing movements in normal and growthretarded fetuses. Am J Obstet Gynecol 153:582, 1985 Vintzileos AM, Campbell WA, Bors-Koefoed R, et al: The relationship between cyclic variation of fetal heart rate patterns and cord pH in preterm gestations. Am J Perinatol. In press Petrikovsky BM, Vintzileos AM, Nochimson DJ: Heart rate cyclicity during labor in healthy term fetuses. Am J Perinatol. In press Petrikovsky BM, Vintzileos AM, Lerer T, Campbell WA: Heart rate cyclicity in preterm fetuses. In press
Downloaded by: University of British Columbia. Copyrighted material.
AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 7, NUMBER 2
