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doi:10.1111/jog.12481
J. Obstet. Gynaecol. Res. Vol. 40, No. 10: 2089–2094, October 2014
Modalities of fetal evaluation to detect fetal compromise prior to the development of significant neurological damage Kazuo Maeda Department of Obstetrics and Gynecology, Tottori University Medical School, Yonago, Japan
Abstract Aims: The aim of this study was to clarify the developmental mechanism underlying fetal heart rate (FHR) long-term variability (LTV) and acceleration with respect to fetal brain damage. Material and Methods: The fetal state was deduced from the developmental mechanism of FHR variability analyzed by actocardiogram, animal experiments, and simulations. Results: LTV develops due to minor fetal movements in the fetal midbrain, moderate LTV by fetal periodic movements and triangular accelerations by large fetal movement bursts. Stimulation of the fetal midbrain by sound and light produces fetal movements that lead to FHR acceleration. Severe hypoxia can result in the loss of LTV and neuronal necrosis that may damage the fetal brain. Therefore, a cesarean section is recommended prior to the loss of LTV, rather than after its loss. The vagal center of the fetal medulla oblongata is excited by hypoxia and produces FHR bradycardia. The heart rate of hypoxic rabbits was found to be closely correlated with the PaO2, thus the impact of hypoxia could be estimated by the hypoxia index, which is calculated from the reciprocal of nadir FHR and bradycardia duration. Conclusions: Analyzing the development of FHR signs could help to diagnose fetal state. An early cesarean section is recommended before the loss of LTV as indicated by the hypoxia index, which will contribute to prevent fetal brain damage and neurological sequels. Key words: development of FHR changes, feial bradycardia, fetal brain damage, fetal movement, hypoxia, loss of FHR variability.
Introduction In recent decades, the frequency of fetal and neonatal deaths has reduced and severe neonatal asphyxia has disappeared.1,2 Herein, we sought to investigate approaches that would lead to a reduction in fetal brain damage and its sequel, studying the developmental mechanism of FHR long-term variability (LTV) and acceleration. The developmental mechanisms that produce FHR patterns have been studied to some degree.3 Additional information can be provided by an actocardiogram,
which is a simultaneous recording of FHR and movement (Fig. 1).5 Such a method could also be used to analyze the developmental processes involved in FHR changes. A non-reactive FHR can be correctly diagnosed when the loss of acceleration is associated with fetal movement bursts. In addition, FHR acceleration is lost, even in the fetal resting state, with no associated fetal movement burst (Fig. 2). In other words, nonreactive FHR develops through the loss of fetal brain responsiveness to fetal movement, such that an investigation of the developmental mechanism of FHR changes is mandatory for a correct FHR diagnosis.
Received: November 28 2013. Accepted: April 23 2014. Reprint request to: Dr Kazuo Maeda, 3-125, Nadamachi, Yonago, Tottori 683-0835, Japan. Email: [email protected]
© 2014 The Author Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
2089
K. Maeda
The cause of non-reassuring fetal status (NRFS) is usually fetal hypoxia that causes two major changes in the fetal central nervous system: (i) it excites the medulla oblongata; and (ii) either suppression of fetal cortical brain or brain damage. Fetal brain suppression and damage is characterized by the loss of FHR acceleration and variability, whereas the stimulated and excited medulla oblongata produces fetal bradycardia via the excitation of the vagal center located in the medulla oblongata. The FHR under hypoxic conditions shows complex patterns because both suppressive and excitatory signals are produced at the same time.
Figure 1 An actocardiogram of the fetal active state. Triangular accelerations are accompanied by frequent fetal movement bursts. Calculation of the A/B ratio of the actocardiogram is illustrated.1,4 FHR, fetal heart rate.
(a)
Methods A common cardiotocogram (CTG)6 is the simultaneous recording of FHR and uterine contraction, whereas an actocardiogram (ACG) is the simultaneous recording of FHR and movements (Fig. 1),5 because CTG cannot clarify the developmental mechanism of FHR acceleration and LTV. An ultrasonic Doppler autocorrelation heart rate meter was therefore used to record the FHR LTV in both CTG and ACG. Fetal movements were also recorded using ultrasonic Doppler recording of fetal chest in the ACG because almost all movements that develop in the fetus are conducted to the fetal chest and can be recorded on an ACG chart, with the exception of fetal facial expressions. Heart rate changes under hypoxic conditions were analyzed in adult female rabbits by simultaneously sampling the rabbit’s blood to determine PaO2.7 The fetal sound stimulation was produced using a quantified 1000 Hz sine wave sound with a loudspeaker, and light stimulation was produced using a photographic flash (GN: 20) on the maternal abdomen.8 The physiological sinusoidal heart rate was differentiated from the true sinusoidal FHR by the presence of physiological periodic fetal respiratory movements.9 The envelope of these movements was compared to the physiological sinusoidal FHR curve. The ACG chart was augmented two to three times to compare LTV with minor fetal movements.10 The ACG of an anencephalic fetus was also analyzed,
(b)
FHR
No movement
AcƟve movements 1 min
Figure 2 (a) Fetal resting state shows no fetal heart rate (FHR) acceleration and no fetal movement. (b) Non-reactive FHR shows no FHR acceleration against active fetal movements.
2090
© 2014 The Author Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Damages in loss of FHR variability
where no acceleration was present against fetal movements, and the LTV amplitude was less than 1 b.p.m. (Fig. 3). A severe late deceleration with the loss of LTV and amplitude less than 1 b.p.m. lasted for 50 min in a NRFS case as a result of the maternal refusal of cesarean section (CS). These data were compared to the anencephalic fetus (Fig. 4). The clinical course of 20 cases of intrauterine growth restriction (IUGR) with actocardiographic non-reactive FHR was compared to those of 20 IUGR fetuses with normal reactive FHR.11 Electronic simulation of FHR
(a)
FHR
Results Fetal sensation stimulation A quantified 1000 Hz sine wave sound stimulation of the fetus for 2 s resulted in fetal movement followed by FHR acceleration.8 Visual stimulation with a flash of light also produced fetal movement followed by FHR acceleration.8 Therefore, the fetal sensation tests produced fetal movement and FHR acceleration in normal fetuses.
(b)
FHR
Movement ContracƟon
acceleration was studied by the passing of grouped signals through an integral circuit with a 7-s time constant.10 The correlation coefficient of FHR and fetal movement signals was largest when the movement signal was delayed for 7 s.12 The adult heart rate change was recorded using an ultrasonic Doppler fetal monitor with repeated continuous leg motions for 1 min as a physiological simulation of FHR acceleration.10
FHR acceleration, moderate variability and LTV Large fetal movement burst provoked triangular FHR acceleration (Fig. 1), periodic fetal respiratory movements developed medium-sized FHR variation (Fig. 5), and the LTV synchronized minor fetal movements.10
ContracƟon
Figure 3 Severe loss of variability of less than 1 b.p.m. (a) Severe late decelerations with the loss of variability. Fetal heart rate (FHR) baseline was the same as an anencephalic fetus. (b) FHR baseline variability of less than 1 b.p.m. in fetal anencephaly.
Electronic simulation of FHR acceleration development The wave groups lasted for 30 s each and were repeatedly input into an integral circuit, with a time constant of 7 s. The outputs were triangular waves similar to FHR acceleration in an electronic simulation.10
FHR
Fetal movements Figure 4 Actocardiogram of an anencephalic fetus, showing neither acceleration against fetal movements nor FHR baseline variability.
ContracƟon
© 2014 The Author Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
2091
K. Maeda
Rabbits’ heart rate (b.p.m.)
7-s delay
1 min
Rabbits’ PaO2 (mmHg) Figure 5 Physiological benign sinusoidal fetal heart rate (FHR) synchonized the envelope of fetal periodic respiratory movements, when the envelope was delayed for 7 s, because the correlation of FHR and fetal movement was largest when the movement was delayed for 7 s.12
Physiological simulation of FHR acceleration An adult heart rate curve, which was recorded during repeated leg motions of 1 min each, developed triangular accelerations similar to FHR acceleration.10 Case of severe late decelerations The FHR baseline of repeated severe late decelerations showed loss of variability with amplitude less than 1 b.p.m. This was the same as the loss of variability in the anencephalic FHR. The neonatal Apgar score was 3 with apnea, which was caused by the loss of respiratory center function. This would be a partial sign of general fetal brain damage (Fig. 3). Actocardiographic non-reactive FHR No acceleration was present against fetal movement bursts in non-reactive IUGR cases but there was preserved LTV (Fig. 2). Some days later, the loss of LTV as well as the bradycardia and/or late decelerations appeared as the NRFS. Emergency CS was performed owing to NRFS, while the outcome was worse than the IUGR cases with reactive FHR to fetal movement.11
Discussion Developmental mechanism of acceleration and LTV in fetal brain An anencephalic fetus showed neither FHR acceleration nor LTV (Fig. 4). Therefore, acceleration and LTV develop in the fetal brain. The neurological locus
2092
Figure 6 A hypoxic rabbit’s heart rate (b.p.m.) was closely correlated to its PaO2, i.e. PaO2 = heart rate × 0.11 + 13.76, R2 = 0.99, P < 0.0017 (modified by Maeda).
responsible for the development of acceleration and LTV is unlikely to be the cortical brain because the triangular heart rate change was not recognized during leg exercise.10 Fetal acceleration develops in the midbrain,13 so the developmental center of FHR acceleration and LTV should be the midbrain. Large fetal movements stimulated FHR acceleration; moderate periodic movements provoked moderate periodic LTV, and small movements developed common LTV in the midbrain.10,13 Intrapartum hypoxia can cause the loss of acceleration and LTV, which are components of the more generalized fetal brain damage that occurs during severe hypoxia. This study focused on the development and disappearance of FHR acceleration and LTV, so that means to avoid fetal brain damage could be identified. The loss of LTV during severe hypoxia precedes fetal brain damage, which would be prevented by delivery of the fetus before the loss of variability, instead of the CS after the loss of variability.
Role of fetal bradycardia FHR bradycardia of less than 110 b.p.m. is a sign of hypoxia, and is caused by excitation of the parasympathetic center by a PaO2 of less than 50 mmHg.6 The bradycardia in rabbits is closely correlated with a PaO2 less than 50 mmHg7 (Fig. 6). FHR bradycardia of less than 110 b.p.m. is indicative of the excitation of medulla oblongata, and thus useful to estimate the impact of hypoxia. Role of acceleration Electronic simulation indicates that the locus of acceleration with an integral system of a 7-s signal delay is
© 2014 The Author Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Damages in loss of FHR variability
the midbrain.13 Large fetal movements develop large acceleration, whereas minor movements develop LTV. Acceleration is lost initially during fetal hypoxia and LTV is preserved in the non-reactive FHR cases, although the LTV is lost with further hypoxia in the NRFS some days later.11 During severe loss of LTV, the amplitude is less than 1 b.p.m. (Fig. 3). However, such a loss is rare in severe hypoxia, which damages the fetal brain as seen in the case of repeated late decelerations and in fetal anencephaly. Therefore, CS is recommended before the loss of LTV to reduce the risk of fetal brain damage and neurological sequels. Acceleration is lost against fetal movement some days before the loss of LTV and NRFS, so that performing a CS at that time can effectively deliver the fetus before the loss of LTV and fetal brain damage.
Proposed hypoxia index to predict the loss of LTV An important question is how to predict the loss of LTV prior to performing a rapid delivery. Actocardiographic non-reactive FHR is an indicative sign for CS,12 but can the loss of LTV be predicted in other situations? A low-amplitude LTV as low as 2–3 b.p.m. may be another indication for CS. As the hypoxic effect is strong when fetal PaO2 is low and of long duration, it can be estimated by taking the reciprocal of PaO2 multiplied by the duration of hypoxia. Unfortunately, fetal PaO2 is hard to measure during labor. The heart rate of a hypoxic rabbit, however, correlated closely with its PaO27 (Fig. 6). Therefore, the hypoxia index can be obtained by dividing hypoxic duration in minutes by the FHR below 110 b.p.m. and multiplying the result by a constant (100). The hypoxia index estimates the effect of hypoxia on the LTV. A CS is recommended when the index is high but below the level before the loss of LTV. The threshold is evident in cases with the loss of LTV or severe hypoxia. Application of the hypoxia index to estimate the hypoxic impact A case of placenta abruption showed sudden 60 b.p.m. bradycardia for 15 min, with a hypoxic index of 25. Another case resulted in brain damage, with a hypoxia index of 25, where there was a severe late deceleration with a nadir of 100 b.p.m. accompanied by the loss of LTV, which lasted for 50 min as a result of maternal refusal of CS. In a case with a hypoxia index of 26, there were severe variable decelerations associated with the loss of LTV before the CS followed by the brain damage with its sequel.
In cases of mild to moderate variable decelerations without the loss of LTV, the hypoxia index was less than 10 in the sum of repeated decelerations. These experiences indicated that the tentative hypoxia index threshold required to perform CS is 20–24. More cases should be investigated to accurately establish this threshold so that there will be effective reduction in the brain damage. The hypoxia index can be automatically obtained in every monitoring by a simple algorithm.
Non-hypoxic FHR abnormalities Abnormal FHR changes have been reported in cases of cytomegalovirus infection14 and in syphilis,15 due to possible damage to the central nervous system. Early delivery and proper treatment of the neonate is therefore also recommended in cases of non-hypoxic FHR abnormalities. Conclusions At present, the loss of long-term FHR variability is an indication for rapid delivery by CS. Analysis of the developmental mechanism of the loss of FHR variability showed that a CS is recommended prior to the loss of FHR variability that can follow fetal brain damage with neurological sequel. High hypoxia index will be an indication for rapid delivery before the loss of FHR variability.
Disclosure No conflict on interest is declared.
References 1. Maeda K, Kimura S, Nakano H et al. Pathophysiology of Fetus. Fukuoka: Fukuoka Printing, 1969; Proc XXI Annual Conv Jap Obstet and Gynecol Society, Kanazawa, 1969. 2. Maeda K. Healthy baby and reduced fetal death by improved obstetric management. In: Karim SMM, Yan KI (eds). Problems in Perinatal Medicine, Proc 1st Asia Oceania Cog Perinatal Medicine. Singapore: Singapore University, 1979; 525–529. 3. Maeda K, Noguchi Y, Matsumoto F, Nagasawa T. Quantitative fetal heart rate evaluation without pattern classification: FHR score and artificial neural network analysis. In: Kurjak A, Chervenak FA (eds). Text Book of Perinatal Medicine, Vol. 2. London: Informa, 2006; 1487–1495. 4. Maeda K, Iwabe T, Ito T et al. Detailed multigrade evaluation of fetal disorders with the quantified actocardiogram. J Perinat Med 2009; 37: 392–396. 5. Maeda K. Studies on new ultrasonic Doppler fetal actograph, and continuous recording of fetal movement. Acta Obstet Gynecol Jpn 1984; 36: 280–288.
© 2014 The Author Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
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6. Hon EH. An Atlas of Fetal Heart Rate Patterns. New Haven: Harty Press, 1968. 7. Umezawa J. Studies on the relation between heart rate and PaO2 in hypoxic rabbit: A comparative study for fetal heart rate change during labor. Acta Obstet Gynecol Jpn 1976; 28: 1203–1212. 8. Tatsumura M, Maeda K, Ito T et al. Studies on features of fetal movement and development of human fetus with use of fetal actocardiogram. Acta Obstet Gynecol Jpn 1991; 43: 864–873. 9. Ito T, Maeda K, Takahashi H et al. Differentiation between physiologic and pathologic sinusoidal FHR pattern by fetal actocardiogram. J Perinat Med 1994; 22: 39–43. 10. Maeda K. Actocardiographic analysis of fetal hypoxia detected by the bradycardia, loss of fetal heart rate acceleration and long term variability. J Health Med Inform 2012; doi org/10.4172/2157-7420.1000118. 11. Teshima N. Non-reactive pattern diagnosed by ultrasonic Doppler fetal actocardiogram and outcome of the fetuses
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12.
13.
14.
15.
with non-reactive pattern. Acta Obstet Gynecol Jpn 1993; 45: 423–430. Takahashi H. Studies on cross correlation coefficient of fetal heart rate and fetal movement signals detected by ultrasonic Doppler fetal actocardiogram. Acta Obstet Gynecol Jpn 1990; 42: 443–449. Terao T, Kawashima Y, Noto H et al. Neurological control of fetal heart rate in 20 cases of anencephalic fetuses. Am J Obstet Gynecol 1984; 140: 201–208. Kaneko M, Sameshima H, Ikeda T, Ikenoue T, Minematsu T. Intrapartum fetal heart rate monitoring in cases of cytomegalovirus infection. Am J Obstet Gynecol 2004; 191: 1257–1262. Kakogawa J, Sadalsuki M, Masuya N, Gomibuchi H, Minoura S, Hoshimoro K. Prolonged fetal bradycardia as the presenting sign in congenital syphilis complicated by necrotizing funisitis: A case report. ISRN Obstet Gynecol 2011; doi: 10.5402/2011/320246.
© 2014 The Author Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
doi:10.1111/jog.12481
J. Obstet. Gynaecol. Res. Vol. 40, No. 10: 2089–2094, October 2014
Modalities of fetal evaluation to detect fetal compromise prior to the development of significant neurological damage Kazuo Maeda Department of Obstetrics and Gynecology, Tottori University Medical School, Yonago, Japan
Abstract Aims: The aim of this study was to clarify the developmental mechanism underlying fetal heart rate (FHR) long-term variability (LTV) and acceleration with respect to fetal brain damage. Material and Methods: The fetal state was deduced from the developmental mechanism of FHR variability analyzed by actocardiogram, animal experiments, and simulations. Results: LTV develops due to minor fetal movements in the fetal midbrain, moderate LTV by fetal periodic movements and triangular accelerations by large fetal movement bursts. Stimulation of the fetal midbrain by sound and light produces fetal movements that lead to FHR acceleration. Severe hypoxia can result in the loss of LTV and neuronal necrosis that may damage the fetal brain. Therefore, a cesarean section is recommended prior to the loss of LTV, rather than after its loss. The vagal center of the fetal medulla oblongata is excited by hypoxia and produces FHR bradycardia. The heart rate of hypoxic rabbits was found to be closely correlated with the PaO2, thus the impact of hypoxia could be estimated by the hypoxia index, which is calculated from the reciprocal of nadir FHR and bradycardia duration. Conclusions: Analyzing the development of FHR signs could help to diagnose fetal state. An early cesarean section is recommended before the loss of LTV as indicated by the hypoxia index, which will contribute to prevent fetal brain damage and neurological sequels. Key words: development of FHR changes, feial bradycardia, fetal brain damage, fetal movement, hypoxia, loss of FHR variability.
Introduction In recent decades, the frequency of fetal and neonatal deaths has reduced and severe neonatal asphyxia has disappeared.1,2 Herein, we sought to investigate approaches that would lead to a reduction in fetal brain damage and its sequel, studying the developmental mechanism of FHR long-term variability (LTV) and acceleration. The developmental mechanisms that produce FHR patterns have been studied to some degree.3 Additional information can be provided by an actocardiogram,
which is a simultaneous recording of FHR and movement (Fig. 1).5 Such a method could also be used to analyze the developmental processes involved in FHR changes. A non-reactive FHR can be correctly diagnosed when the loss of acceleration is associated with fetal movement bursts. In addition, FHR acceleration is lost, even in the fetal resting state, with no associated fetal movement burst (Fig. 2). In other words, nonreactive FHR develops through the loss of fetal brain responsiveness to fetal movement, such that an investigation of the developmental mechanism of FHR changes is mandatory for a correct FHR diagnosis.
Received: November 28 2013. Accepted: April 23 2014. Reprint request to: Dr Kazuo Maeda, 3-125, Nadamachi, Yonago, Tottori 683-0835, Japan. Email: [email protected]
© 2014 The Author Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
2089
K. Maeda
The cause of non-reassuring fetal status (NRFS) is usually fetal hypoxia that causes two major changes in the fetal central nervous system: (i) it excites the medulla oblongata; and (ii) either suppression of fetal cortical brain or brain damage. Fetal brain suppression and damage is characterized by the loss of FHR acceleration and variability, whereas the stimulated and excited medulla oblongata produces fetal bradycardia via the excitation of the vagal center located in the medulla oblongata. The FHR under hypoxic conditions shows complex patterns because both suppressive and excitatory signals are produced at the same time.
Figure 1 An actocardiogram of the fetal active state. Triangular accelerations are accompanied by frequent fetal movement bursts. Calculation of the A/B ratio of the actocardiogram is illustrated.1,4 FHR, fetal heart rate.
(a)
Methods A common cardiotocogram (CTG)6 is the simultaneous recording of FHR and uterine contraction, whereas an actocardiogram (ACG) is the simultaneous recording of FHR and movements (Fig. 1),5 because CTG cannot clarify the developmental mechanism of FHR acceleration and LTV. An ultrasonic Doppler autocorrelation heart rate meter was therefore used to record the FHR LTV in both CTG and ACG. Fetal movements were also recorded using ultrasonic Doppler recording of fetal chest in the ACG because almost all movements that develop in the fetus are conducted to the fetal chest and can be recorded on an ACG chart, with the exception of fetal facial expressions. Heart rate changes under hypoxic conditions were analyzed in adult female rabbits by simultaneously sampling the rabbit’s blood to determine PaO2.7 The fetal sound stimulation was produced using a quantified 1000 Hz sine wave sound with a loudspeaker, and light stimulation was produced using a photographic flash (GN: 20) on the maternal abdomen.8 The physiological sinusoidal heart rate was differentiated from the true sinusoidal FHR by the presence of physiological periodic fetal respiratory movements.9 The envelope of these movements was compared to the physiological sinusoidal FHR curve. The ACG chart was augmented two to three times to compare LTV with minor fetal movements.10 The ACG of an anencephalic fetus was also analyzed,
(b)
FHR
No movement
AcƟve movements 1 min
Figure 2 (a) Fetal resting state shows no fetal heart rate (FHR) acceleration and no fetal movement. (b) Non-reactive FHR shows no FHR acceleration against active fetal movements.
2090
© 2014 The Author Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Damages in loss of FHR variability
where no acceleration was present against fetal movements, and the LTV amplitude was less than 1 b.p.m. (Fig. 3). A severe late deceleration with the loss of LTV and amplitude less than 1 b.p.m. lasted for 50 min in a NRFS case as a result of the maternal refusal of cesarean section (CS). These data were compared to the anencephalic fetus (Fig. 4). The clinical course of 20 cases of intrauterine growth restriction (IUGR) with actocardiographic non-reactive FHR was compared to those of 20 IUGR fetuses with normal reactive FHR.11 Electronic simulation of FHR
(a)
FHR
Results Fetal sensation stimulation A quantified 1000 Hz sine wave sound stimulation of the fetus for 2 s resulted in fetal movement followed by FHR acceleration.8 Visual stimulation with a flash of light also produced fetal movement followed by FHR acceleration.8 Therefore, the fetal sensation tests produced fetal movement and FHR acceleration in normal fetuses.
(b)
FHR
Movement ContracƟon
acceleration was studied by the passing of grouped signals through an integral circuit with a 7-s time constant.10 The correlation coefficient of FHR and fetal movement signals was largest when the movement signal was delayed for 7 s.12 The adult heart rate change was recorded using an ultrasonic Doppler fetal monitor with repeated continuous leg motions for 1 min as a physiological simulation of FHR acceleration.10
FHR acceleration, moderate variability and LTV Large fetal movement burst provoked triangular FHR acceleration (Fig. 1), periodic fetal respiratory movements developed medium-sized FHR variation (Fig. 5), and the LTV synchronized minor fetal movements.10
ContracƟon
Figure 3 Severe loss of variability of less than 1 b.p.m. (a) Severe late decelerations with the loss of variability. Fetal heart rate (FHR) baseline was the same as an anencephalic fetus. (b) FHR baseline variability of less than 1 b.p.m. in fetal anencephaly.
Electronic simulation of FHR acceleration development The wave groups lasted for 30 s each and were repeatedly input into an integral circuit, with a time constant of 7 s. The outputs were triangular waves similar to FHR acceleration in an electronic simulation.10
FHR
Fetal movements Figure 4 Actocardiogram of an anencephalic fetus, showing neither acceleration against fetal movements nor FHR baseline variability.
ContracƟon
© 2014 The Author Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
2091
K. Maeda
Rabbits’ heart rate (b.p.m.)
7-s delay
1 min
Rabbits’ PaO2 (mmHg) Figure 5 Physiological benign sinusoidal fetal heart rate (FHR) synchonized the envelope of fetal periodic respiratory movements, when the envelope was delayed for 7 s, because the correlation of FHR and fetal movement was largest when the movement was delayed for 7 s.12
Physiological simulation of FHR acceleration An adult heart rate curve, which was recorded during repeated leg motions of 1 min each, developed triangular accelerations similar to FHR acceleration.10 Case of severe late decelerations The FHR baseline of repeated severe late decelerations showed loss of variability with amplitude less than 1 b.p.m. This was the same as the loss of variability in the anencephalic FHR. The neonatal Apgar score was 3 with apnea, which was caused by the loss of respiratory center function. This would be a partial sign of general fetal brain damage (Fig. 3). Actocardiographic non-reactive FHR No acceleration was present against fetal movement bursts in non-reactive IUGR cases but there was preserved LTV (Fig. 2). Some days later, the loss of LTV as well as the bradycardia and/or late decelerations appeared as the NRFS. Emergency CS was performed owing to NRFS, while the outcome was worse than the IUGR cases with reactive FHR to fetal movement.11
Discussion Developmental mechanism of acceleration and LTV in fetal brain An anencephalic fetus showed neither FHR acceleration nor LTV (Fig. 4). Therefore, acceleration and LTV develop in the fetal brain. The neurological locus
2092
Figure 6 A hypoxic rabbit’s heart rate (b.p.m.) was closely correlated to its PaO2, i.e. PaO2 = heart rate × 0.11 + 13.76, R2 = 0.99, P < 0.0017 (modified by Maeda).
responsible for the development of acceleration and LTV is unlikely to be the cortical brain because the triangular heart rate change was not recognized during leg exercise.10 Fetal acceleration develops in the midbrain,13 so the developmental center of FHR acceleration and LTV should be the midbrain. Large fetal movements stimulated FHR acceleration; moderate periodic movements provoked moderate periodic LTV, and small movements developed common LTV in the midbrain.10,13 Intrapartum hypoxia can cause the loss of acceleration and LTV, which are components of the more generalized fetal brain damage that occurs during severe hypoxia. This study focused on the development and disappearance of FHR acceleration and LTV, so that means to avoid fetal brain damage could be identified. The loss of LTV during severe hypoxia precedes fetal brain damage, which would be prevented by delivery of the fetus before the loss of variability, instead of the CS after the loss of variability.
Role of fetal bradycardia FHR bradycardia of less than 110 b.p.m. is a sign of hypoxia, and is caused by excitation of the parasympathetic center by a PaO2 of less than 50 mmHg.6 The bradycardia in rabbits is closely correlated with a PaO2 less than 50 mmHg7 (Fig. 6). FHR bradycardia of less than 110 b.p.m. is indicative of the excitation of medulla oblongata, and thus useful to estimate the impact of hypoxia. Role of acceleration Electronic simulation indicates that the locus of acceleration with an integral system of a 7-s signal delay is
© 2014 The Author Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Damages in loss of FHR variability
the midbrain.13 Large fetal movements develop large acceleration, whereas minor movements develop LTV. Acceleration is lost initially during fetal hypoxia and LTV is preserved in the non-reactive FHR cases, although the LTV is lost with further hypoxia in the NRFS some days later.11 During severe loss of LTV, the amplitude is less than 1 b.p.m. (Fig. 3). However, such a loss is rare in severe hypoxia, which damages the fetal brain as seen in the case of repeated late decelerations and in fetal anencephaly. Therefore, CS is recommended before the loss of LTV to reduce the risk of fetal brain damage and neurological sequels. Acceleration is lost against fetal movement some days before the loss of LTV and NRFS, so that performing a CS at that time can effectively deliver the fetus before the loss of LTV and fetal brain damage.
Proposed hypoxia index to predict the loss of LTV An important question is how to predict the loss of LTV prior to performing a rapid delivery. Actocardiographic non-reactive FHR is an indicative sign for CS,12 but can the loss of LTV be predicted in other situations? A low-amplitude LTV as low as 2–3 b.p.m. may be another indication for CS. As the hypoxic effect is strong when fetal PaO2 is low and of long duration, it can be estimated by taking the reciprocal of PaO2 multiplied by the duration of hypoxia. Unfortunately, fetal PaO2 is hard to measure during labor. The heart rate of a hypoxic rabbit, however, correlated closely with its PaO27 (Fig. 6). Therefore, the hypoxia index can be obtained by dividing hypoxic duration in minutes by the FHR below 110 b.p.m. and multiplying the result by a constant (100). The hypoxia index estimates the effect of hypoxia on the LTV. A CS is recommended when the index is high but below the level before the loss of LTV. The threshold is evident in cases with the loss of LTV or severe hypoxia. Application of the hypoxia index to estimate the hypoxic impact A case of placenta abruption showed sudden 60 b.p.m. bradycardia for 15 min, with a hypoxic index of 25. Another case resulted in brain damage, with a hypoxia index of 25, where there was a severe late deceleration with a nadir of 100 b.p.m. accompanied by the loss of LTV, which lasted for 50 min as a result of maternal refusal of CS. In a case with a hypoxia index of 26, there were severe variable decelerations associated with the loss of LTV before the CS followed by the brain damage with its sequel.
In cases of mild to moderate variable decelerations without the loss of LTV, the hypoxia index was less than 10 in the sum of repeated decelerations. These experiences indicated that the tentative hypoxia index threshold required to perform CS is 20–24. More cases should be investigated to accurately establish this threshold so that there will be effective reduction in the brain damage. The hypoxia index can be automatically obtained in every monitoring by a simple algorithm.
Non-hypoxic FHR abnormalities Abnormal FHR changes have been reported in cases of cytomegalovirus infection14 and in syphilis,15 due to possible damage to the central nervous system. Early delivery and proper treatment of the neonate is therefore also recommended in cases of non-hypoxic FHR abnormalities. Conclusions At present, the loss of long-term FHR variability is an indication for rapid delivery by CS. Analysis of the developmental mechanism of the loss of FHR variability showed that a CS is recommended prior to the loss of FHR variability that can follow fetal brain damage with neurological sequel. High hypoxia index will be an indication for rapid delivery before the loss of FHR variability.
Disclosure No conflict on interest is declared.
References 1. Maeda K, Kimura S, Nakano H et al. Pathophysiology of Fetus. Fukuoka: Fukuoka Printing, 1969; Proc XXI Annual Conv Jap Obstet and Gynecol Society, Kanazawa, 1969. 2. Maeda K. Healthy baby and reduced fetal death by improved obstetric management. In: Karim SMM, Yan KI (eds). Problems in Perinatal Medicine, Proc 1st Asia Oceania Cog Perinatal Medicine. Singapore: Singapore University, 1979; 525–529. 3. Maeda K, Noguchi Y, Matsumoto F, Nagasawa T. Quantitative fetal heart rate evaluation without pattern classification: FHR score and artificial neural network analysis. In: Kurjak A, Chervenak FA (eds). Text Book of Perinatal Medicine, Vol. 2. London: Informa, 2006; 1487–1495. 4. Maeda K, Iwabe T, Ito T et al. Detailed multigrade evaluation of fetal disorders with the quantified actocardiogram. J Perinat Med 2009; 37: 392–396. 5. Maeda K. Studies on new ultrasonic Doppler fetal actograph, and continuous recording of fetal movement. Acta Obstet Gynecol Jpn 1984; 36: 280–288.
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