An approach to the study of brain damage

FETUS, PLACENTA, AND NEWBORN

An approach to the study of brain damage The principles

of fetal electroencephalography

MORTIMER

G.

JOSEPH LAWRENCE

M.D.

CHIK,

AGNETA Rochester,

M.D.

ROSEN,

SCIBETTA,

D. New

PH.D.

BORGSTEDT,

M.D.

York

Fetal electroencephalography (EEG) is technically feasible and has been alterations found accomplished in more than 300 monitored fetuses. The ekctrical are identifiable both in individual fetuses and between different fetuses. These patterns and changes can be differentiated from pre-existing patterns and associated with certain fetal cardiovascular heart rate changes. The preliminary follow-up findings on a small group of infants followed until one year of life are presented. The information presented here should be used as guidelines for the introduction of this technique rather than answers to the problems of clinical monitoring during birth and the relationship of that monitoring to brain damage,

bodies differences in both technique of use and principles of interpretation when compared to the classical use of EEG. The purpose of this report is to delineate the differences as well as to establish criteria for the understanding of this research tool. In the hypothesis proposed at the beginning of the fetal monitoring program, it was stated that the fetal EEG would be a time marker of stressful events during labor as they are reflected in the electrical energy of the fetal brain. This report is based on monitoring studies involving more than 300 fetuses during labor. Important in these results are the preliminary data of an infant follow-up program. The results of the program suggest basic standards for use in clinical research and guidelines for interpreting the fetal tracings.

ELECTROENCEPHALOGRAPHY

(EEG) is a laboratory technique used in assessing central nervous system abnormality. Fetal EEG is a new application of this laboratory test. Intrapartum EEG em-

From the Fetal Brain Research Laboratory, Department of Obstetrics and Gynecology,.University of Rochester, School of Medrcrne and Dentistry. Supported Foundation, Foundation,

by the John A. Hartford Inc., and the Grant Inc.

Received

for publication

May

Accepted 1972.

for publication

August

26, 1972. 18,

Reprint requests: Mortimer G. Rosen, M.D., Dept. of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, 260 Crittenden Boulevard, Rochester, New York 14642. 37

38

Rosen

et al.

Fig. 1. Fetal surface of electrode, cradled in hand, showing prominent central EEG recording point and the smaller ECG sensor on the electrode rim. Material

and

methods

Technical fetal EEG. The electrode measures2.5 cm. in diameter. Two electrodes are inserted sequentially through the cervix that will admit one finger. A central silver pin has replaced the previously reported needle point (Fig. 1). l, 2 The silver pin is reusable, doesnot bend, and allows one to advance the electrodes along the fetal scalp without resistance. Neither the previously reported needle-point model nor this present sensor has resulted in more than superficial fetal scalp abrasionsfollowing their use. The amniotic membranes must be ruptured so that the sensormakes direct contact with the fetal scalp. When the electrode is placed inside the cervix against the fetal scalp, suction is applied (10 to 15 inches Hg). This suction maintains a stable recording platform and minimizes movement artifacts during maternal uterine contractions (Fig. 2, A and B). The suction also aids in isolating the central recording point. Without this isolation,

the

highly

conductive

amniotic

fluid

and skin vernix may lead to attenuation of

the electrical potentials between the two recording points. In addition, when the recording points are exposed, the much higher amplitude fetal heart signals (Fig. 3, A, B, and C) contaminate the tracing and render that study useless. A recording is considered useless if the fetal electrocardiogram (EGG) contaminates it in amounts equal to or more than the visible EEG voltages. Fetal heart contamination is the major reason for failure of a monitoring study, yet the reasons for ECG presence at the sensors are not completely understood. Importance of recording sites. The experienced clinician can usually determine the recording site of each electrode after he applies it. Areas of scalp erythema or abrasion may be more easily visible about 24 hours post partum and will allow both interelectrode recording distance and scalp locations to be recorded. Interelectrode recording distance is important. If this distance is less than 4 cm., it may result in a low voltage pattern which must be differentiated from an “abnormal” low voltage recording (Fig. 4). Also, due to different rates of fetal brain maturation, the central or parietal areas over the skull record electrical activity more clearly than low occipital or temporal regions. The latter areas are slower to mature and electrically appear more “silent.” Therefore, if one recording point is not parietal in location, the recording must be interpreted cautiously. The fetal technique compared to nonobstetric EEG techniques. The classical electroencephalographer locates montages of ten to twenty electrodes at specific anatomical sites on the scalp. In this manner, the electrical activity observed is more representative of the underlying cortex and may discretely define areas of the brain in which pathology is located. The application of large numbers of electrodes is impractical in fetal recording. With digital manipulation, the two electrodes may be moved to opposite sides of the sagittal suture, but their sites will vary in each application and from patient to patient. Once in place, however,

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Fig. 2. A. Normal, movement artifacts ment. Most of the

Fig. 3. tude of artifact for an

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39

acceptable, and useful EEG which is free of artifact. B, Large base-line during a uterine contraction are indicative of an unstable electrode piacesecond half of this line is unacceptable for evaluation.

A, Normal, acceptable, and useful EEG. B, Heartbeat artifact almost equal the brain wave tracing. This ECG artifact is at the limit of a useful record. contaminates the tracing, rendering it useless for evaluation. This is the unacceptable tracing.

to the ampliC, This ECG major reason

A

Fig. 4. A, Low-voltage recording occipital in location. B, Appropriate

which shows only ECG. The sensors were 3 cm. voltage in well-spaced biparietal sensor location.

they are not easily dislodged and one may be certain that continuous recording is coming from the same site. As noted earlier, parietal location is desired since this area overlies the most mature cortex with easily discernible EEG patterns. On several occasions, three sensors have been used. At present the information gained from the additional sensor does not warrant its use. Therefore, cvith these noted differences, it beromes apparent that fetal EEG may be used as a general monitor which reflects large brain areas but is not useful in defin-

ing or locating discrete age may be found.

apart

and

areas in which

dam-

Results

The observations made are the results of more than 300 successfully monitored fetuses during the past three years. Our over-all success rate for obtaining useful readings is slightly above 50 per cent, but certain individuals may be more successful based on experience and persistence their acquired in the application until all recording criteria are met, All physicians in our obstet-

40

Rosen

Jammy 1, 197: Am. J. Obstet. Gynecol

et al.

FM 140

FHR 110

FHR 40

FNR 120

Fig. 5. A, FHR 140. Normal tracing in amplitude 110. Shortly after onset of cardiac deceleration

and

frequency

prior

to deceleration.

B, FHR

slow waves (1 and % cycles per second) of

higher amplitude (75 to 100 pv) appear. C, FHR 70. Near lowest point of cardiac deceleration isoelectric intervals appear. D, FHR 60. Essentially no EEG activity present when compared to Line A. E, FHR 120. EEG almost identical to Line A. There is an increase in slower waves (3 to 5 cycles per second) which disappear when the FHR returns to 140.

ric training program apply these electrodes. In addition, a program is underway in which nurses apply the same EEG and intrauterine pressure (IUP) recording sensors. During labor, two general situations are described. The first category is a series of events transient in time, related to a specific clinical event occurring at that moment, and in which the electrical changes do not persist after the termination of that single event. These events would best be labeled as “transient.” The second major category is a descfiption of wave forms or voltages which are persistent and seemingly less influenced by the acute events occurring during labor. These are described as “nontransient” fetal EEG events. They are present at the start, or early in the monitoring study, and persist through major portions of the recording. The terms “transient” and “nontransient” refer only to EEG seen during the period of monitoring.

Transient fetal EEG changes during patterns of cardiac deceleration. The EEG has been observed during periodic fetal heart rate decelerations. The definitions for these patterns are based on the publications of Hon.3 The characteristic fetal EEG changes are first depicted in Fig. 5. From a preexisting pattern present prior to the onset of the heart rate depression (Fig. 5, A), the EEG appears to lose the faster rhythms, followed by more apparent slowing (Fig. 5, B). Next are the isoelectric or almost flat periods (Fig. 5, C) interspersed with rare bursts of EEG, and finally there is a totally isoelectric interval (Fig. 5, D) . This latter interval will last more than 10 seconds and is clearly different from the patterns observed in the presence of burstsuppression EEG activity or following the use of medication. As the heart rate returns to its base-line rate, the reverse of this progression takes place. The isoelectric pattern is replaced by

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HearI Rote

A (can’t.)

Fig. 6. Variable Arrow correlated

decelerations. (Note with next 18 seconds

different of EEG

calibration changing

scales for IUP, to almost isoelectric

FHR, and recording.

EEG.)

Fig. 7. Delayed deceleration. (Note different calibration scales for IUP, FHR, and EEG.) Arrow at A indicates next 9 seconds of EEG early in the delayed deceleration as EEG begins to become isoelectric. Arrow at B later in delayed deceleration shows an isoelectric 9 second interval.

occasional and then more persistent electrical activity (Fig. 5, E) . Prior to the onset of the next uterine contraction, the EEG voltages and wave frequencies will have returned to their pre-existing visually described states. The entire sequence, from onset to return, may last from 30 seconds to longer than one minute. As noted above, the isoelectric period alone is longer than 10 seconds, but its duration will depend on the length of the associated cardiac events.

Most isoelectric periods do not last more than 30 seconds. These periodic EEG changes are noted in Fig. 6 (variable deceleration) and Fig. 7 (delayed deceleration). Since EEG paper recording speeds are 30 mm. per second and ECG-IUP paper speeds are much slower at 30 mm. per minute, only 10 seconds of EEG recording are displayed as samples of the isoelectric moments. How(Fig. 5)) these are a ever, as described

42

Rosen

et al.

Janrrar~ I, 19i:i Am.

J. Ohstrt.

Cynecol

kort Rote

Fig. 8. Early deceleration. (Note different calibration scales for FHR, IUP, and EEG.) Arrows at A and B at low point of decelerations without loss of significant EEG voltages. continuum of changes beginning with easily visible EEG patterns, reaching the almost straight-line isoelectric interval and then reversing this progression back to the preexisting EEG picture. Transient EEG changes appear frequently during these fetal heart rate alterations. However, we do not yet have the data to state that these cardiovascular and central nervous system observations are always associated with each other. Several reasons for this difficulty in correlation exist. A 4 hour EEG recording at 30 mm. per second is over 43 meters long. Some recordings may last 12 hours. It is impractical (visually) to compare all this information to the slower speed IUP-fetal heart rate (FHR) trace with more than casual accuracy. In addition, the word descriptions of the periodic fetal heart rate decelerations do not easily lend themselves to digital analysis. Often, combinations of such FHR patterns make for some difficulty in visual identification or mathematical description. Therefore, while we can state that these EEG changes are often synchronous with some of these deceleration curves, we cannot state this is always so, and we cannot as yet sort out which times the EEG does not alter with these two heart rate deceleration patterns. In contrast to variable and delayed heart rate patterns, EEG changes are generally

not seen in those situations defined as “early deceleration.“3 These latter decelerative FHR changes seen during both the course of labor and most often the second stage of labor and maternal “bearing down” do not show EEG isoelectricity (Fig. 8). Transient EEG changes during forceps application. In a pilot project, electrodes were left in place during forceps rotation and traction.” In several cases, the forceps traction pressure was measured with the use of a traction handle (Fig. 9). From these studies it can be seen that transient EEG changes do occur during traction and rotation. The EEG appears to revert to normal patterns after the delivery or when the forceps are unlocked and pressure is released prior to birth. As noted in Fig. 9, the visual picture of the neonatal EEG is quite similar to that seen prior to the forceps application. Nontransient EEG changes-sharp waves. have been seen in these “Sharp waves” recordings. They can be defined as repetitive waves always in the same polarity (during that recording), generally higher in amplitude than surrounding EEG, and generally being less than 50 msec. in duration. When observed, they were present most often at the onset of the recordings and continued throughout labor. They must be clearly distinguished from spindlelike wave forms and sharp theta waves often seen in the course of burst-suppression activity. These wave

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I

Fig. 9. Forceps

and the EEG. A, EEG prior to forceps application. B, Forceps blades are in place. C, EEG begins to change in this case at 25 mm. Hg of traction pressure as measured at forceps handle. D, Despite relaxation of forceps traction, FHR remains depressed and EEG is isoelectric. E, Transient elevation of FHR. The EEG remains isoelectric. F, Immediately after birth. The neonatal EEG is quite similar to previous fetal recording prior to forceps traction.

forms are distinct from burst-suppression activity and generally occur during periods of relative EEG silence. They are not associated with maternal medications. In the first cases noted, they were associated with neonatal convulsions and necessitated anticonvulsive medication (Fig. 10, A). This directed our attention to their observation and documentation. Most often, they are not associated with an abnormal neonatal clinical picture (Fig. 10, B and C) but appear more frequently in the developmentally abnormal child seen at one year of life. This is described in the section under follow-up results and in Tables I and II. Nontransient EEG changes-low voltage recordings. As discussed earlier, one must insure adequate electrode location before classifying the EEG as a low-voltage recording. The persistence of all recording voltages below 20 ,uv lvith prolonged intervals of isoelectricity (distinct from the rapidly changing picture described under cardiac decelera-

tion) is described as a low-voltage tracing. Two clinical pictures have been seen. The first is seen in association with normal amplitude and pattern of recording which in the course of labor changes to persistent low voltage with prolonged periods of isoelectricity (Fig. 11) , This clinical picture is described with more certainty because of the pre-existing normal patterns which change under direct observation. Clinically, this is more often seen in the less mature infant in the presence of analgesic medications. It would appear that small infants reflect medication most sensitively with EEG events. In Fig. 11, this term infant was delivered with a normal Apgar score but reverted to a lethargic state when not stimulated. Several of these infants have suffered respiratory apnea and postpartum aspiration, necessitating intensive care. The postnatal clinical behavior of these infants is predictable from the visual scanning of the EEG. The second low-voltage picture is that

44

Rosen

et al. Am.

J.

January 1, 1973 Obstet. Gynecol.

Fig. 10. A, Note calibration. Arrow indicates sharp wave seen prior to onset of uterine contractions. Labor was then stimulated with oxytocin. This infant convulsed during the first 24 hours of life. B, Sharp waves seen throughout labor. This infant is developmentally abnormal at one year of age. C, Sharp waves seen throughout labor. This infant has not yet been seen for his one-year examination.

which is seen from the onset of recording and persists through delivery. Again, ensuring adequate electrode location and comparing this trace with the neonatal recording lends more credence to this diagnosis. Within this described electrical picture, we have found several of the more critically ill infants (Fig. 12)) including two hydrocephalic infants and one premature infant who died in the neonatal period. This finding would seem to indicate an already stressed infant prior to the onset of monitoring and perhaps prior to labor. Preliminary

follow-up

report

In Table I, 8 infants studied at the end of one year and one infant who died neonatally are presented. These infants were abnormal in neurologic development at the time of that examination. The use of infants with only obvious abnormal clinical developmental findings at one year was an important aid in identifying predictive fetal EEG criteria for use in a prospective study. Since pre-existing standards for reading this information were not available, it seemed most logical to attempt to set these standards based on developmental information. Sharp waves as defined earlier were recorded in 5 of these infants. Low voltage

of the persistent pattern was seen in 6 cases. In 5 of these cases, both sharp waves and low voltage were seen. In Table II, 27 infants found to be normal at the end of one year are presented. In this group, the presence of sharp waves is infrequent, occurring 3 times in a total of 27 infants. The low-voltage picture seen so frequently in the abnormal population occurred twice in this same group of 27 infants. The combination of low voltage and sharp waves did not occur in the normal population. This clinical follow-up is of necessity preliminary in nature, since at the onset of the program definitions relating to sharp waves, low voltages, and transient and nontransient EEG changes were not known. These definitions were developed only with time, the rereading of these early EEG’s, and association with clinical infant developmental studies. Twenty-four infants at the end of one year are not clearly either normal or abnormal. They (as well as the reported populations) continue to be evaluated in the follow-up program. This is necessary since not all developmental problems are identifiable at one year of age. Many of the infants in both populations the “transient” EEG also experienced changes

in

association

with

heart

rate

de-

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I. Abnormal

Gestational (weeks)

age

34 37 40 39 42 36* 37 40 40 NR = not recorded. *Neonatal death.

Table

II. Normal

Gestational (weeks)

age

37 38 40 40 NR 35 40 36 40 3’ 40 40 41 40 41 40 36 41 33 40 39 40 40 40 40 41 44 NR

=

not recorded.

infants

Apgar

I

score

1 min.

0 = Not

EEG 5 min.

5 8 8 8 7 5 9 5 6

+ = Present.

Sharp

NR 10 9 10 NR 8 10 7 NR

waves

Low-voltage

+ + + ;I

:, c $ +

; 0 +

?I i +

present.

at one year of age Apgar

Weight (Gm.)

1 min.

2,440 3,300 3,260 3,220 2,780 2,200 3,400 3,110 3,400 2,600 3,380 3,800 2,620 3,410 3,100 3,360 3,440 3,430 2,010 3,520 3,800 3,650 2,780 3,650 3,140 3,920 3,460 + = Present.

45

at one year of age

Weight (Cm.) 1,940 2,640 2,760 2,640 3,650 1,840 2,340 3,370 4,340

infants

to study of brain damage

i i 7 9 9 a : a 8 9 9 9” 4 6 9 8 9 8 9 5 9 6 4 0 = Not

EEG

score 5 min. 9 10 9 9 9 10 10 9 9 10 NR 10 10 9 9 10 9 9 9 10 10 10 9 9 10 8 5

Sharp

waves 0 0 0’ 0 0 0 ii 0 0 0 0 0 0 0 0 0 0 0 0 0 ; 0 0 0

Low-voltage 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 o* 0 0 0 0 0 0 0 0 f

present.

celerations. The obstetric histories for these cases included multiple pre-existing clinical problems such as toxemia, diabetes, and prematurity as well as intrapartum observations of meconium or audible fetal heart rate variations suggesting a fetus at risk. The EEG was obtained but not used in fetal management. The obstetrician responsible for his patient continued to direct the patient’s medical management with the use of the additional FHR and IUP information. A more detailed description of the antecedent obstet-

ric events is not presented at this time since the population is too small to have meaning in this area. The infants’ weights, gestational ages, and Apgar scores are listed in Tables I and II. In these categories, there are no marked differences between our normal and abnormal populations. Comment The introduction of a new technique is a step taken with hesitancy and caution. Fetal EEG was first attempted with abdominal

46

Rosen

et al.

Fig. 11. A, Early tinued

recording the birth.

through

of term

fetus.

B,

Persistent

lower

voltage

recording

which

con-

of almost flat EEG from start to end of recording in infant B, Neonatal recording shows some increased amplitude but of patterns throughout entire recording period.

later with-

A

WI 1SK

B

Fig. 12. A, Fetal

recording found to be hydrocephalic. out appropriate organization

recordings by Lindsley5 and later vaginally by Bernstine and associates.‘j Yet, without appropriate recording techniques, the limited use of EEG even as a research tool remained inadequate. The tracings obtained by early investigators did not resemble neonatal recordings in the same infants or in other infants of similar birth weights. In 1969, with the use of appropriate recording techniques, fetal monitoring of EEG became practical.*, i We now know that the fetal or neonatal electroencephalogram relates to maturity and is unchanged by the electrical normal birth process. 1v2* 7 Sudden

the characteristics of EEG after birth, fetal EEG monitoring becomes a new measure potentially useful in the study of brain damage. The results, as described earlier, are related to ongoing labor events and also suggest stresses pre-existing labor. While watching a tracing, one may observe a fetal pattern rapidly change to a flat or isoelectric state. This situation exists, based on more than 300 studies, and its repetitive presence in certain labors becomes clear. The analogue to this state in the adult exists in the extrauterine state during transient syncopal episodes with rapid loss of consciousness. However, the

brain

repetitive

events

do

not

take

place

with

the

first

breath.. The EEG reader must be familiar with neonatal recordings and how they vary with infant maturity. There are marked differences in fetal recordings of infants weighing 1,500 grams and those weighing 3,500 grams.” And, as in the neonate, criteria for normality will vary with maturity. In the presence of an adequate recording technique and a base-line understanding of

character

of

these

changes

in

a

rapidly maturing organism has no known adult counterpart. Even in the adult, isoelectric EEG may be associated with an unconscious state, yet these episodes may not be associated with cerebral damage if adequate circulation persists. In fetus

a

recent

used

as

publication an

with

analogue

fetus, Myers9 describes

repetitive

of

the the

rhesus human

fetal stresses

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such as fetal bradycardia (described as late cardiac decelerations) associated with low blood pressure and pathophysiologic metabolic changes resulting in a small number of surviving monkeys who exhibited permanent brain damage. No monitoring of the rhesus fetal brain electroencephalogram was performed; therefore, no inferences can be made beyond the fact that someof these surviving infants exhibited anatomical brain damage. The second major group of EEG alterations, described in this report as “nontransient” changes, appears to antedate birth and to relate to developmental clinical abnormality at the end of one year of life. It is suspected but not proved that these conditions antedate the labor period, In two cases associated with low voltage, hydrocephalus was recognized within 3 days after birth with enlarged head circumference measurements. The association of both low-voltage EEG and sharp waves appears frequently enough in the abnormal population to warrant further study. The steps leading to the sorting out of those antepartum situations which are etiologic factors in the course of brain damage are complicated by our lack of specific knowledge in this area. Certain individual etiologic causes of brain damage can be implicated, such as kernicterus, but these cases are in the minority. The situation is further confused not only by the multiple factors which must be considered but also by the

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critical periods of brain growth prior to birth. TowbinlO suggeststhat four types of fetal cerebral lesionsare found and relate to mechanical and hypoxic stressesand that the cerebral locus for the later expression of any such stressesis directly influenced by gestational age (i.e., that time in development when the stressoccurred). The investigator in human fetal studies of cerebral morbidity finds that clinical neurological function is difficult to define clearly immediately after birth and tedious developmental study must continue at least until the child has had someopportunity for intellectual expression. The use of fetal EEG as a research tool is presented here as a technique with welldocumented electrical observations but with clinical correlations which need further study. The test itself would seem to document some events occurring prior to labor as well as electrical events occurring during labor. When used as a laboratory tool in this manner, more information may be brought to bear on the etiology of brain damage and its prevention. If this fetal monitor can predict the later appearance of developmental abnormality, then it becomesa valuable tool not only for etiologic study and prevention but also for the identification and early treatment of potentially brain-damaged infants. Appreciation is expressedto Mrs. Margaret Steinbrecher and Mr. Leonard Braun for their excellent technical assistance.

REFERENCES

1. Rosen,M. G., and Scibetta, J. J.: AM. J. OBSTET.

GYNECOL.

104: 1057, 1969.

2. Rosen,M. G., Scibetta, J. J., and Hochberg, C. J.: Obstet. Gynecol. 36: 132, 1970. 3. Han, E. H.: An Atlas of FetaI Heart Rate Patterns,New Haven, 1968,Harty Press,Publishers. 4. Hochberg, C. J,, Scibetta, J. J. and Rosen, M. G.: Unpublisheddata. 5. Lindsley, D. B.: Am. J. Psychol. 55: 412, 1942. 6. Bernstine,R. L., Borkowski,W. J., and Price, A. H.: AM. J. OBSTET. GYNECOL. 70: 623, 1955. 7. Rosen,M. G., and Scibetta, J. J.: Neuropadiatrie 2: 17, 1970.

8. Dreyfus-Brisac,C.: The electroencephalogram of the prematureinfant and full-term newborn: Normal and abnormaldevelopmentof waking and sleepingpatterns,in Neurological and Electroencephalographic CorrelativeStudies in Infancy, New York, 1964, Grune & Stratton, Inc. 9. Myers, R. E.: AM. J. OBSTET. GYNECOI.. 112: 246, 1972. 10. Towbin, A.: Am. J. Dis. Child. 119: 529, 1970. 11. Prechtl, H., and Beintema,D.: The Neuroloeical Examination of the Full-Term Newbovn Infant, London, 1964, William Heinemann Ltd., Publishers.