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Antepartum fetal heart rate response to sound stimulation: The acoustic stimulation test
FHR accelerations at 38 to 40 weeks' gestation
Volume 148 Number I
5. 6.
7.
8. 9. 10.
tum fetal heart rate testing, AM. J. OBSTET. GYNECOL. 137:983, 1980. Brown, R., and Patrick, J.: The nonstress test: How long is enough? AM. j. 0BSTET. GYNECOL. 141:646, 1981. Patrick, J., Campbell, K.., Carmichael, L., Natale, R., and Richardson, B.: Patterns of gross fetal body movements over 24-hour observation intervals during the last 10 weeks of pregnancy, AM. J. OBSTET. GYNECOL. 142:363, 1982. Patrick,]., Campbell, K., Carmichael, L., and Probert, C.: Influence of maternal heart rate and gross fetal body movements on the daily pattern of fetal heart rate near term, AM. J. OssTET. GYNECOL. 144:533, 1982. Bailey, N. T. J.: Statistical Methods in Biology, London, 1964, English Universities Press, p. 50. Wheeler, T., and Murrills, A.: Patterns of fetal heart rate during normal pregnancy, Br. J. Obstet. Gynaecol. 85:18, 1978. Sorokin, Y., Dierker, L. J., Chik, L., Kollar, L. L., and Rosen, M. G.: Fetal heart rate accelerations in low-risk
11. 12. 13. 14.
15.
and diabetic pregnancies during active behavioral periods, AM.J. 0BSTET. GYNECOL. 143:224, 1982. Merkur, H.: Normal and abnormal antenatal ultrasonic cardiographic patterns, Br. J. Obstet. Gynaecol. 86:533, 1979. Lee, C., and Drukker, B.: The nonstress test for the antepartum assessment of fetal reserve, AM. J. 0BSTET. GYNECOL. 134:460, 1979. Wheeler, T., and Guerard, P.: Fetal heart rate during late pregnancy, J. Obstet. Gynaecol. Br. Commonw. 84:348, 1974. Visser, G. H. A., Dawes, G. S., and Redman, G. H. A., Dawes, G. S., and Redman, C. W. G.: Numerical analysis of the normal human antenatal fetal heart rate, Br. J. Obstet. Gynaecol. 88:792, 1981. Timor-Tritsch, I. E., Dierker, L. J., Zadar, I., Hertz, R. H., and Rosen, M.G.: Fetal movements associated with fetal heart rate accelerations and decelerations, AM. J. 0BSTET. GYNECOL. 131:276, 1978.
Antepartum fetal heart rate response to sound stimulation: The acoustic stimulation test Paulo Serafini, M.D., Mary B. J. Lindsay, M.D., David A. Nagey, M.D., Ph.D., Marcos J. Popkin, M.D., Paul Tseng, M.D., and Carlyle Crenshaw, Jr., M.D. Baltimore, Maryland The fetal heart rate acceleration response to an acoustic stimulation was compared to the traditional nonstress test in regard to pregnancy outcome, as reflected by the incidence of intrapartum fetal distress, meconium staining of the amniotic fluid, 1- and 5-minute Apgar scores, and perinatal mortality. Fetuses with spontaneous or sound-generated reactivity had comparably good outcomes with respect to all outcome measures investigated. Fetuses who lacked spontaneous or sound-stimulated reactivity had an increased risk for intrapartum fetal distress. The acoustic stimulation test is a safe and rapid test of fetoplacental sufficiency that appears to perform comparably to the nonstress test. The acoustic stimulation test significantly shortens total antepartum testing time and expense. (AM. J. OBSTET. GYNECOL. 148:41, 1984.)
During the past several years, there has been increasing reliance upon the nonstress test rather than on serial measurements of urinary or serum estriol or the contraction stress test for the purpose of determining the health of the fetus in utero. 1- 4 The reactive nonstress test is a reliable indicator of fetal well-being, although the hypoactive, sleq.. ng, or "medicated" fetus may take as long as 80 minutes to demonstrate reactivFrom the Department of Obstetrics and Gynecology, University of Maryland School of Medicine and Hospital. Presented in part at the Thirtieth Annual Meeting of the Society for Gynecologic Investigation, Washington, D. C., March 17-20, 1983. Received for publication April27, 1983. Accepted August 17, 1983. Reprint requests: Dr. Marcos ]. Pupkin, Department of Obstetrics and Gynecology, University of Maryland School of Medicine and Hospital, 22 South Greene St., Baltimore, Maryland 21201.
ity. 4 - 7 Read and MillerS were the first to explore the use of a pure tone auditory stimulus in the antenatal evaluation of the conceptus. Trudinger and Boylan 4 observed that sound stimulation of the fetus is a rapid procedure that requires only 10 minutes and that an impaired fetal heart rate response had a positive predictive value greater than that of a nonreactive nonstress test. Zugaib and Behle 5 abbreviated nonstress testing time by using acoustic stimuli to convert half of the hypoactive patterns to reactive patterns. The present study compares the use of the fetal heart rate acceleration response to an auditory stimulus to the traditional nonstress test in regard to pregnancy outcome, as reflected by the incidence of intrapartum fetal distress, meconium staining of the amniotic fluid, !-minute and 5-minute Apgar scores, and perinatal mortality. 41
42 Serafini et al. Am.
L
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January 1, 1984
J. Obstet. Gynecol.
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Fig. 1. A reactive acoustic stimulation test tracing.
Material and methods
Antepartum biophysical fetal testing (nonstress test, acoustic stimulation test, contraction stress test) was performed 439 times in 233 patients followed in the High Risk Obstetric Clinic of the University of Maryland Hospital. These tests comprised 439 nonstress tests, 438 acoustic stimulation tests, and 4 7 contraction stress tests. The indications for testing are listed in Table I. Patients were properly counseled, and informed consent was obtained prior to application of the sound stimulus. The acoustic stimulation test involved an acoustic stimulus generated by a simple oscillating amplifier and delivered via a 3 inch speaker placed on the maternal abdomen in the region of the fetal head. Four 1-second pulses separated by 1-second intervals were applied. The pulses were of 1 ,220 Hz frequency and had a sound pressure level of 126 dB measured in air at 1 em from the generating source by a real-time spectrum analyzer (FFT 512/s Rockland System Co.). The sound pressure levels usually employed in acoustic testing (100 to 130 dB) are comparable in intensity to maternal vascular noise and borborygmi 9 when the 45 dB (approximate) acoustic absorption of the uterus and maternal abdominal wall are taken into account. 10 Fetal heart rate recordings were carried out with an external ultrasound transducer and tocodynamometer (Corometrics, Model 111). Ten minutes were required for the performance of the acoustic stimulation test: 5 minutes of monitoring prior to the sound stimulus and 5 minutes afterward. The criteria for assessing acoustic stimulation test, nonstress test, and contraction stress test results are given in Table II. A reactive acoustic stimulation test is shown in Fig. 1. Acoustic stimulation tests were performed on those patients who had nonstress tests, who agreed to par-
Table I. Indications for antenatal testing* % Postdates Diagnosed/suspected intrauterine growth retardation Hypertension/ preeclampsia Diabetes mellitus History of stillbirth Decreased fetal movement Other
73 61
45
58 36
36
23
15
42
38
22
14
9
26
*Total is not 100% since some patients had multiple indications.
ticipate. Contraction stress tests were performed in response to nonreactive nonstress tests irrespective of acoustic stimulation test results. Physicians who cared for these patients acted upon the results of the nonstress test and contraction stress test in the conventional manner. Although they were not blinded to the acoustic stimulation test tracing, they were not instructed as to how to interpret it. All antepartum and intrapartum tracings were interpreted by one of the authors (P. S.) without knowledge of the pregnancy outcome. Fetal distress in labor was defined as an abnormal fetal heart rate recording with late decelerations occurring after more than 30% of the contractions in any stage of labor, consistently severe variable decelerations followed by poor recovery, or absence of fetal heart rate variability (less than 5 bpm by internal fetal monitoring). Apgar scores were assigned by trained delivery room or nursery personnel, without knowledge of the antepartum test results. No cesarean sections were performed because of a nonreactive nonstress test or a positive contraction stress test. When one considers only the tests performed within
Antepartum FHA response to sound
Volume 148 Number I
Table IV. Incidence of intrapartum distress
Table II. Criteria for grading nonstress test, acoustic stimulation test, and contraction stress test
Test
Reactive nonstress test2 : Two accelerations of the fetal heart rate,
each at least 15 bpm for 15 seconds within any 20-minute interval, in association with fetal movement or uterine contraction Nonreactive nonstress test2 : Failure to achieve a reactive nons tress test within 40 minutes despite fetal manipulation Reactive acoustic stimulation test": Fetal heart rate acceleration of at least 15 bpm for at least 120 seconds or two accelerations of at least 15 bpm for at least 15 seconds within 5 minutes of the stimulus Nonreactive acoustic stimulation test8 : Inability to fulfill either criterion for reactivity as listed above within 5 minutes Negative contraction stress test 1: No fetal heart rate decelerations despite three uterine contractions in 10 minutes Positive contraction stress test 1: Fetal heart rate late decelerations after at least two thirds of the contractions
Table III. Results of the last test prior to delivery when done within 7 days of delivery Test
Nonstress test (n = 161) Reactive Nonreactive Unsatisfactory Acoustic stimulation test (n = 160) Reactive Nonreactive Unsatisfactory Contraction stress test (n = 25) Negative Positive Unsatisfactory
43
No.
%
141 20 0
87.6 12.4 0
132 27 1
82.5 16.9 0.6
16 7 2
64.0 28.0 8.0
7 days of delivery, there were 161 nonstress tests, 160 acoustic stimulation tests, and 2 5 contraction stress tests. From this point onward, only these results will be evaluated. The incidence of primary cesarean section in the reactive-nonstress test group was 9/141 (6.4%), contrasted with 8/132 (6.1%) in the reactive-acoustic stimulation test group. (p = NS). The data obtained were analyzed for statistical significance by the standard x2 test with continuity corrections where appropriate (cell size s5).
Results Of the 161 nonstress tests, 141 (87.6%) were reactive, and 20 (12.4%) were nonreactive. One hundred thirtytwo (82.5%) of the 160 acoustic stimulation tests were reactive, whereas 27 (16.9%) were nonreactive, and only one acoustic stimulation test (0.6%) was unsatisfactory. Of the 2 5 contraction stress tests, 16 (64 .0%) were negative, seven (28.0%) were positive, and two (8.0%) were unsatisfactory. These data are summarized in Table Ill. The difference between the rates of reactiv-
Nonstress test Reactive Nonreactive Acoustic stimulation test Reactive Nonreactive Contraction stress test Negative Positive
%
No.
>* > >
18/141 14/20
171132 14/27 5116 5/7
*
t
12.8 70 12.9 51.8 31.2 71.4
The nons tress test and the acoustic stimulation test are statistically indistinguishable with respect to intrapartum distress. *p < 0.001. tp < 0.05.
ity for the nonstress test (87.6%) and the acoustic stimulation test (82.5%), as well as nonreactivity for the nonstress test (12.4%) and the acoustic stimulation test (16.9%) was not significant. Intrapartum fetal distress occurred in 18 of 141 (12.8%) spontaneously reactive fetuses and in 17 of 132 (12.9%) sound-reactive conceptuses. This difference was not significant. The rates of fetal distress in the group of nonreactive fetuses, 14 of 20 nonstress tests (70.0%) and 14 of27 acoustic stimulation tests (51.8%), were significantly higher than those in the reactive fetuses (p < 0.001 ), but the intertest difference was not significant. The incidence of fetal distress in labor is listed in Table IV. The incidence of cesarean section for fetal distress is not reported because of unavoidable bias as well as the subjectivity of the diagnosis. However, the incidence was comparable between tests. None of the biophysical tests, neither the nonstress test, the acoustic stimulation test, nor the contraction stress test, could predict low 1- and 5-minute Apgar scores, or meconium staining of the amniotic fluid. As can be seen from Tables V and VI, these tests performed comparably; indeed, the x2 test was not significant in all cases. Antepartum fetal death was observed in one Instance. In this case the patient had chronic hypertension and a history of a child with multiple congenital malformations; a 50% abruptio placentae occurred at 39 weeks' gestation, 2 days after both the nonstress test and acoustic stimulation test were reactive. One neonatal death occurred in an adolescent patient admitted at 28 weeks' gestation for prolonged spontaneous rupture of membranes. Biophysical evaluation was begun on a twice weekly basis. Both the nonstress test and acoustic stimulation test were reactive 6 days prior to delivery, and both tests were nonreactive 2 days prior to delivery. Labor was induced because of chorioamnionitis, and the patient was deliv-
44 Serafini et al.
January 1, 1984 Am. ]. Obstet. Gynecol.
Table VI. Incidence of nonvigorous fetuses (Apgar scores of 0 to 6 at 1 and 5 minutes)
Table V. Incidence of meconium in the amniotic fluid Test
Nonstress test Reactive Nonreactive Acoustic stimulation test Reactive Nonreactive Contraction stress test Negative Positive
No.
%
27/121 4/15
22.3 26.7
25/112 5/22
22.3 22.7
3/14 1/4
21.4 25.0
The denominators differ from those used in other tables since there were no data on the presence or absence of meconium in some patients. ered (vaginally) of a I ,300 gm infant with Apgar scores of I and 6. A labor fetal heart rate tracing revealed fetal distress characterized by fetal heart rate tachycardia (180 bpm), severe variable decelerations, and a lack of variability (two to three bpm). This neonate developed severe respiratory distress syndrome and died 3 days after birth. The autopsy revealed intraventricular hemorrhage and atelectatic lungs with histologic evidence of hyaline membrane disease. Comment
A rapid and predictable antenatal screening test is of great value in the assessment of the fetus at risk. The response of the fetus to a sound stimulus as an indicator of the fetal status has been contemplated since late I920s. 11 Sontag and Wallace 12 observed that the human fetus was able to respond to certain vibratory stimuli by an increase in heart rate. In I947, Sontag and Bernard 1" used the fetal cardiac response to a loud noise as an index of fetal reactivity. An acceleration of the fetal heart rate with an application of I ,000 and 2,000 Hz stimuli with a sound pressure level of IOO dB was reported by Dwornicka and coworkers. 14 Grimwade and associates 15 validated previous observations by demonstrating a definite acceleration of the fetal heart to sound stimulus. Murphy and Smyth, 16 in their evaluation of two diabetic patients, noted a conversion in the fetal heart rate response to sound, from reactive to nonreactive, 4 weeks prior to the delivery of stillborn infants. Read and Miller, 8 using a 2,000 Hz (I05 to I20 dB) stimulus observed that when the fetal heart rate acceleration evoked exceeded 15 bpm the subsequent contraction stress test was always negative and pregnancy outcome was good. Trudinger and Boylan 4 reported a greater discriminatory value for the acoustic stimulation test than for the nonstress test in detecting fetal compromise. The hypoactive, nonreactive fetuses who experienced a change to a reactive pattern upon application of sound had a good outcome, in the experience of Zugaib and Behle. 5
Test
No.
%
20/141 4/20
14.2 20.0
17/132 7/27
12.0 25.9
l/16 217
6.3 36.4
4/141 1/20
2.8 5.0
4/132 l/27
3.0 3.7
0/16 017
0 0
1 min Apgar score 0-6
Nonstress test Reactive Nonreactive Acoustic stimulation test Reactive Nonreactive Contraction stress test Negative Positive
5 min Apgar score 0-6
Nonstress test Reactive Nonreactive Acoustic stimulation test Reactive Nonreactive Contraction stress test Negative Positive
The results of the present study revealed a comparable incidence of spontaneous and sound-generated reactivity when tests were performed within 7 days of delivery. The occurrences of intrapartum distress, with the use of a strict definition of electronic distress (as set forth in Material and methods), were essentially the same in both reactive groups (12.8% and I2.9%) (Table IV). The incidence of meconium and the incidence of nonvigorous infants (Apgar scores of :56 at 5 minutes) were not significantly different when reactive nonstress tests and acoustic stimulation tests were compared and when nonreactive nonstress tests and acoustic stimulation tests were compared. These data demonstrate comparable predictive value of the reactive nonstress test and the reactive acoustic stimulation test with respect to the outcome measures evaluated. The results obtained are in agreement with the data reported by Trudinger and Boylan 4 and by Zugaib and Behle. 5 In summary, the acoustic stimulation test is a safe, rapid test of fetoplacental sufficiency that appears to perform comparably to the traditional nonstress test. We are continuing to correlate perinatal outcome with acoustic stimulation test results to be sure that acoustic stimulation test performance can withstand the scrutiny of thousands of patients. We wish to thank David Saar of Black and Decker Corporation for the sound pressure level measurements. REFERENCES 1. Keane, M. W. D., Horger, E. 0., and Vice, L.: Comparative study vf stressed and nonstressed antepartum fetal heart rate testing, Obstet. Gynecol. 57:320, 1981. 2. Druzin, M.D., Gratacos,J., and Paul, R. H.: Antepartum fetal heart rate testing. VI. Predictive reliability of "nor-
Volume 148 Number 1
3. 4. 5. 6. 7. 8. 9. 10. 11.
mal" tests in the prevention of antepartum death, AM.]. 0BSTET. GYNECOL. 137:746, 1980. Rayburn, W., Zuspan, F., Mootley, M.D., and Donaldson, M.: An alternative to antepartum fetal heart rate testing, AM.]. 0BSTET. GYNECOL. 138:223, 1980. Trudinger, B. J., and Boylan, P.: Antepartum fetal heart rate monitoring: Value of sound stimulation, Obstet. Gynecol. 55:265, 1980. Zugaib, M., and Behle, 1.: Antepartum stress test, in Fetal Monitoring, ed. 1, Sao Paulo, Brazil, 1981, Roca. Brown, R., and Patrick, J.: The nonstress test: How long is enough? AM.]. 0BSTET. GYNECOL. 141:646, 1981. Paul, R. H., and Miller, F. C.: Antepartum fetal heart rate monitoring, Clin. Obstet. Gynecol. 21:375, 1978. Read,]. A., and Miller, F. C.: Fetal heart rate acceleration in response to acoustic stimulation as a measure of fetal well-being, AM.j. 0BSTET. GYNECOL. 129:512, 1977. Henshall, W. R.: Intrauterine sound levels, AM. J. OBSTET. GYNECOL. 112:576, 1972. Walker, D., Grimwade, J., and Wood, C.: Intrauterine noise: A component of the fetal environment, AM. J. 0BSTET. GYNECOL. 109:91, 1971. Forbes, H. S., and Forbes, H. B.: Fetal sense reactions: Hearing,]. Comp. Psycho!. 7:353, 1927.
Antepartum FHR response to sound
12. Sontag, L. W., and Wallace, R. F.: Changes in the rate of the human fetal heart response to vibratory stimuli, Am. ]. Dis. Child. 51:583, 1936. 13. Sontag, L. W., and Bernard, J.: Fetal reactivity to tonal stimulation: A preliminary report, J. Gen. Psycho!. 70: 205, 1947. 14. Johansson, B., Wedenberg, E., and Westin, B.: Measurement of tone response by the human foetus, Acta Otolaryngol. 57:188, 1964. 15. Grimwade,J. C., Walker, D. W., Bartlett, M., Gordon, S., and Wood, C.: Human fetal heart rate change and movement in response to sound and vibration, AM. J. 0BSTET. GYNECOL. 109:86, 1971. 16. Murphy, K. P., and Smyth, C. N.: Response of fetus to auditory stimulation, Lancet 1:1972, 1962. 17. Slomka, C., and Phelan,]. P.: Pregnancy outcome in the patient with a nonreactive nonstress test and a positive contraction stress test, AM.]. OBSTET. GYNECOL. 139:11, 1981. 18. Keegan, K. A., and Paul, R. H.: Antepartum fetal heart rate testing. IV. The nonstress test as a primary approach, AM. j. 0BSTET. GYNECOL. 136:75, 1980.
Production of active and acid-activated renin by cultured explants of human fetal tissues A. Y. Warren, D. J. Craven, and E. M. Symonds Nottingham, England Various fetal tissues with gestational ages that ranged from 6 to 22 weeks were cultured as explants, and the culture media were examined for the production of both active and acid-activated renin. Media from cultures of fetal kidney, both the male and female genital tracts, and umbilical cord vessels were found to contain large quantities of active and acid-activated renin. Consistent differences in the production patterns of renin were found between the tissues, which may reflect the different potentials of the tissues to produce renin in vivo. (AM. J. 0BSTET. GYNECOL. 148:45, 1984.)
The discovery of high concentrations of renin in human amniotic fluid' prompted the investigation of the female genital tract as a possible site of renin synthesis. Myometrium and chorion laeve were found to contain and be capable of synthesizing large amounts of renin in vitro. 2 • :l It would appear, however, that uterine sources of renin may be more important at a local level, rather than in the general circulation, since renin activity levels reported in uterine venous plasma were not invariably elevated compared to peripheral levels. 4 Two forms of renin have been described-active From the Department of Obstetrics and Gynaecology, University Hospital, Queens Medical Centre. Received for publicaton February 11, 1983. Revised june 6, 1983. Accepted july 12, 1983. Reprint requests: Dr. E. M. Symonds, Department of Obstetrics and Gynaecology, University Hospital, Queens Medical Centre, Nottingham, NG7 2UH, England.
renin, which reacts with its substrate at a physiologic pH, and an acid-activated renin, inactive at a normal pH." Recent studies have implicated tissue kallikreins to be the physiologic activators of inactive renin, 6 thereby indicating that renin may function locally in specific tissues, producing angiotensin II close to its site of action. The presence of active and acid-activated renin in the human female genital tract and the production in vitro of both forms of renin by specific tissues' enhance the possibility of a local role for the renin-angiotensin system in the female genital tract. In this study, we investigated the potential synthesis of renin by various fetal tissues, in an attempt to assess the contribution of fetal renin to the maternal pool and the importance of fetal renin production in utero.
Material and methods Tissues were collected from six patients who underwent termination of pregnancy between 6 and 22
45
Volume 148 Number I
5. 6.
7.
8. 9. 10.
tum fetal heart rate testing, AM. J. OBSTET. GYNECOL. 137:983, 1980. Brown, R., and Patrick, J.: The nonstress test: How long is enough? AM. j. 0BSTET. GYNECOL. 141:646, 1981. Patrick, J., Campbell, K.., Carmichael, L., Natale, R., and Richardson, B.: Patterns of gross fetal body movements over 24-hour observation intervals during the last 10 weeks of pregnancy, AM. J. OBSTET. GYNECOL. 142:363, 1982. Patrick,]., Campbell, K., Carmichael, L., and Probert, C.: Influence of maternal heart rate and gross fetal body movements on the daily pattern of fetal heart rate near term, AM. J. OssTET. GYNECOL. 144:533, 1982. Bailey, N. T. J.: Statistical Methods in Biology, London, 1964, English Universities Press, p. 50. Wheeler, T., and Murrills, A.: Patterns of fetal heart rate during normal pregnancy, Br. J. Obstet. Gynaecol. 85:18, 1978. Sorokin, Y., Dierker, L. J., Chik, L., Kollar, L. L., and Rosen, M. G.: Fetal heart rate accelerations in low-risk
11. 12. 13. 14.
15.
and diabetic pregnancies during active behavioral periods, AM.J. 0BSTET. GYNECOL. 143:224, 1982. Merkur, H.: Normal and abnormal antenatal ultrasonic cardiographic patterns, Br. J. Obstet. Gynaecol. 86:533, 1979. Lee, C., and Drukker, B.: The nonstress test for the antepartum assessment of fetal reserve, AM. J. 0BSTET. GYNECOL. 134:460, 1979. Wheeler, T., and Guerard, P.: Fetal heart rate during late pregnancy, J. Obstet. Gynaecol. Br. Commonw. 84:348, 1974. Visser, G. H. A., Dawes, G. S., and Redman, G. H. A., Dawes, G. S., and Redman, C. W. G.: Numerical analysis of the normal human antenatal fetal heart rate, Br. J. Obstet. Gynaecol. 88:792, 1981. Timor-Tritsch, I. E., Dierker, L. J., Zadar, I., Hertz, R. H., and Rosen, M.G.: Fetal movements associated with fetal heart rate accelerations and decelerations, AM. J. 0BSTET. GYNECOL. 131:276, 1978.
Antepartum fetal heart rate response to sound stimulation: The acoustic stimulation test Paulo Serafini, M.D., Mary B. J. Lindsay, M.D., David A. Nagey, M.D., Ph.D., Marcos J. Popkin, M.D., Paul Tseng, M.D., and Carlyle Crenshaw, Jr., M.D. Baltimore, Maryland The fetal heart rate acceleration response to an acoustic stimulation was compared to the traditional nonstress test in regard to pregnancy outcome, as reflected by the incidence of intrapartum fetal distress, meconium staining of the amniotic fluid, 1- and 5-minute Apgar scores, and perinatal mortality. Fetuses with spontaneous or sound-generated reactivity had comparably good outcomes with respect to all outcome measures investigated. Fetuses who lacked spontaneous or sound-stimulated reactivity had an increased risk for intrapartum fetal distress. The acoustic stimulation test is a safe and rapid test of fetoplacental sufficiency that appears to perform comparably to the nonstress test. The acoustic stimulation test significantly shortens total antepartum testing time and expense. (AM. J. OBSTET. GYNECOL. 148:41, 1984.)
During the past several years, there has been increasing reliance upon the nonstress test rather than on serial measurements of urinary or serum estriol or the contraction stress test for the purpose of determining the health of the fetus in utero. 1- 4 The reactive nonstress test is a reliable indicator of fetal well-being, although the hypoactive, sleq.. ng, or "medicated" fetus may take as long as 80 minutes to demonstrate reactivFrom the Department of Obstetrics and Gynecology, University of Maryland School of Medicine and Hospital. Presented in part at the Thirtieth Annual Meeting of the Society for Gynecologic Investigation, Washington, D. C., March 17-20, 1983. Received for publication April27, 1983. Accepted August 17, 1983. Reprint requests: Dr. Marcos ]. Pupkin, Department of Obstetrics and Gynecology, University of Maryland School of Medicine and Hospital, 22 South Greene St., Baltimore, Maryland 21201.
ity. 4 - 7 Read and MillerS were the first to explore the use of a pure tone auditory stimulus in the antenatal evaluation of the conceptus. Trudinger and Boylan 4 observed that sound stimulation of the fetus is a rapid procedure that requires only 10 minutes and that an impaired fetal heart rate response had a positive predictive value greater than that of a nonreactive nonstress test. Zugaib and Behle 5 abbreviated nonstress testing time by using acoustic stimuli to convert half of the hypoactive patterns to reactive patterns. The present study compares the use of the fetal heart rate acceleration response to an auditory stimulus to the traditional nonstress test in regard to pregnancy outcome, as reflected by the incidence of intrapartum fetal distress, meconium staining of the amniotic fluid, !-minute and 5-minute Apgar scores, and perinatal mortality. 41
42 Serafini et al. Am.
L
!
1
1
7
I
1, 1 ,
11
i
I
I rf
.t [I r: c0 c~· 0 r r r c0 cG0 0 oTo II 0 0.Dll c. G0 a0u~u 0 0 0 0 0 0 J 0 0 0 oto 0 0 0 0
-i}f
J
1
L. ~
UAU
January 1, 1984
J. Obstet. Gynecol.
I
....,
UA
0 0 0 0 J 0 0 0 0 0 1 0 .il a11 o1JJ 11 J
I I
·~
Fig. 1. A reactive acoustic stimulation test tracing.
Material and methods
Antepartum biophysical fetal testing (nonstress test, acoustic stimulation test, contraction stress test) was performed 439 times in 233 patients followed in the High Risk Obstetric Clinic of the University of Maryland Hospital. These tests comprised 439 nonstress tests, 438 acoustic stimulation tests, and 4 7 contraction stress tests. The indications for testing are listed in Table I. Patients were properly counseled, and informed consent was obtained prior to application of the sound stimulus. The acoustic stimulation test involved an acoustic stimulus generated by a simple oscillating amplifier and delivered via a 3 inch speaker placed on the maternal abdomen in the region of the fetal head. Four 1-second pulses separated by 1-second intervals were applied. The pulses were of 1 ,220 Hz frequency and had a sound pressure level of 126 dB measured in air at 1 em from the generating source by a real-time spectrum analyzer (FFT 512/s Rockland System Co.). The sound pressure levels usually employed in acoustic testing (100 to 130 dB) are comparable in intensity to maternal vascular noise and borborygmi 9 when the 45 dB (approximate) acoustic absorption of the uterus and maternal abdominal wall are taken into account. 10 Fetal heart rate recordings were carried out with an external ultrasound transducer and tocodynamometer (Corometrics, Model 111). Ten minutes were required for the performance of the acoustic stimulation test: 5 minutes of monitoring prior to the sound stimulus and 5 minutes afterward. The criteria for assessing acoustic stimulation test, nonstress test, and contraction stress test results are given in Table II. A reactive acoustic stimulation test is shown in Fig. 1. Acoustic stimulation tests were performed on those patients who had nonstress tests, who agreed to par-
Table I. Indications for antenatal testing* % Postdates Diagnosed/suspected intrauterine growth retardation Hypertension/ preeclampsia Diabetes mellitus History of stillbirth Decreased fetal movement Other
73 61
45
58 36
36
23
15
42
38
22
14
9
26
*Total is not 100% since some patients had multiple indications.
ticipate. Contraction stress tests were performed in response to nonreactive nonstress tests irrespective of acoustic stimulation test results. Physicians who cared for these patients acted upon the results of the nonstress test and contraction stress test in the conventional manner. Although they were not blinded to the acoustic stimulation test tracing, they were not instructed as to how to interpret it. All antepartum and intrapartum tracings were interpreted by one of the authors (P. S.) without knowledge of the pregnancy outcome. Fetal distress in labor was defined as an abnormal fetal heart rate recording with late decelerations occurring after more than 30% of the contractions in any stage of labor, consistently severe variable decelerations followed by poor recovery, or absence of fetal heart rate variability (less than 5 bpm by internal fetal monitoring). Apgar scores were assigned by trained delivery room or nursery personnel, without knowledge of the antepartum test results. No cesarean sections were performed because of a nonreactive nonstress test or a positive contraction stress test. When one considers only the tests performed within
Antepartum FHA response to sound
Volume 148 Number I
Table IV. Incidence of intrapartum distress
Table II. Criteria for grading nonstress test, acoustic stimulation test, and contraction stress test
Test
Reactive nonstress test2 : Two accelerations of the fetal heart rate,
each at least 15 bpm for 15 seconds within any 20-minute interval, in association with fetal movement or uterine contraction Nonreactive nonstress test2 : Failure to achieve a reactive nons tress test within 40 minutes despite fetal manipulation Reactive acoustic stimulation test": Fetal heart rate acceleration of at least 15 bpm for at least 120 seconds or two accelerations of at least 15 bpm for at least 15 seconds within 5 minutes of the stimulus Nonreactive acoustic stimulation test8 : Inability to fulfill either criterion for reactivity as listed above within 5 minutes Negative contraction stress test 1: No fetal heart rate decelerations despite three uterine contractions in 10 minutes Positive contraction stress test 1: Fetal heart rate late decelerations after at least two thirds of the contractions
Table III. Results of the last test prior to delivery when done within 7 days of delivery Test
Nonstress test (n = 161) Reactive Nonreactive Unsatisfactory Acoustic stimulation test (n = 160) Reactive Nonreactive Unsatisfactory Contraction stress test (n = 25) Negative Positive Unsatisfactory
43
No.
%
141 20 0
87.6 12.4 0
132 27 1
82.5 16.9 0.6
16 7 2
64.0 28.0 8.0
7 days of delivery, there were 161 nonstress tests, 160 acoustic stimulation tests, and 2 5 contraction stress tests. From this point onward, only these results will be evaluated. The incidence of primary cesarean section in the reactive-nonstress test group was 9/141 (6.4%), contrasted with 8/132 (6.1%) in the reactive-acoustic stimulation test group. (p = NS). The data obtained were analyzed for statistical significance by the standard x2 test with continuity corrections where appropriate (cell size s5).
Results Of the 161 nonstress tests, 141 (87.6%) were reactive, and 20 (12.4%) were nonreactive. One hundred thirtytwo (82.5%) of the 160 acoustic stimulation tests were reactive, whereas 27 (16.9%) were nonreactive, and only one acoustic stimulation test (0.6%) was unsatisfactory. Of the 2 5 contraction stress tests, 16 (64 .0%) were negative, seven (28.0%) were positive, and two (8.0%) were unsatisfactory. These data are summarized in Table Ill. The difference between the rates of reactiv-
Nonstress test Reactive Nonreactive Acoustic stimulation test Reactive Nonreactive Contraction stress test Negative Positive
%
No.
>* > >
18/141 14/20
171132 14/27 5116 5/7
*
t
12.8 70 12.9 51.8 31.2 71.4
The nons tress test and the acoustic stimulation test are statistically indistinguishable with respect to intrapartum distress. *p < 0.001. tp < 0.05.
ity for the nonstress test (87.6%) and the acoustic stimulation test (82.5%), as well as nonreactivity for the nonstress test (12.4%) and the acoustic stimulation test (16.9%) was not significant. Intrapartum fetal distress occurred in 18 of 141 (12.8%) spontaneously reactive fetuses and in 17 of 132 (12.9%) sound-reactive conceptuses. This difference was not significant. The rates of fetal distress in the group of nonreactive fetuses, 14 of 20 nonstress tests (70.0%) and 14 of27 acoustic stimulation tests (51.8%), were significantly higher than those in the reactive fetuses (p < 0.001 ), but the intertest difference was not significant. The incidence of fetal distress in labor is listed in Table IV. The incidence of cesarean section for fetal distress is not reported because of unavoidable bias as well as the subjectivity of the diagnosis. However, the incidence was comparable between tests. None of the biophysical tests, neither the nonstress test, the acoustic stimulation test, nor the contraction stress test, could predict low 1- and 5-minute Apgar scores, or meconium staining of the amniotic fluid. As can be seen from Tables V and VI, these tests performed comparably; indeed, the x2 test was not significant in all cases. Antepartum fetal death was observed in one Instance. In this case the patient had chronic hypertension and a history of a child with multiple congenital malformations; a 50% abruptio placentae occurred at 39 weeks' gestation, 2 days after both the nonstress test and acoustic stimulation test were reactive. One neonatal death occurred in an adolescent patient admitted at 28 weeks' gestation for prolonged spontaneous rupture of membranes. Biophysical evaluation was begun on a twice weekly basis. Both the nonstress test and acoustic stimulation test were reactive 6 days prior to delivery, and both tests were nonreactive 2 days prior to delivery. Labor was induced because of chorioamnionitis, and the patient was deliv-
44 Serafini et al.
January 1, 1984 Am. ]. Obstet. Gynecol.
Table VI. Incidence of nonvigorous fetuses (Apgar scores of 0 to 6 at 1 and 5 minutes)
Table V. Incidence of meconium in the amniotic fluid Test
Nonstress test Reactive Nonreactive Acoustic stimulation test Reactive Nonreactive Contraction stress test Negative Positive
No.
%
27/121 4/15
22.3 26.7
25/112 5/22
22.3 22.7
3/14 1/4
21.4 25.0
The denominators differ from those used in other tables since there were no data on the presence or absence of meconium in some patients. ered (vaginally) of a I ,300 gm infant with Apgar scores of I and 6. A labor fetal heart rate tracing revealed fetal distress characterized by fetal heart rate tachycardia (180 bpm), severe variable decelerations, and a lack of variability (two to three bpm). This neonate developed severe respiratory distress syndrome and died 3 days after birth. The autopsy revealed intraventricular hemorrhage and atelectatic lungs with histologic evidence of hyaline membrane disease. Comment
A rapid and predictable antenatal screening test is of great value in the assessment of the fetus at risk. The response of the fetus to a sound stimulus as an indicator of the fetal status has been contemplated since late I920s. 11 Sontag and Wallace 12 observed that the human fetus was able to respond to certain vibratory stimuli by an increase in heart rate. In I947, Sontag and Bernard 1" used the fetal cardiac response to a loud noise as an index of fetal reactivity. An acceleration of the fetal heart rate with an application of I ,000 and 2,000 Hz stimuli with a sound pressure level of IOO dB was reported by Dwornicka and coworkers. 14 Grimwade and associates 15 validated previous observations by demonstrating a definite acceleration of the fetal heart to sound stimulus. Murphy and Smyth, 16 in their evaluation of two diabetic patients, noted a conversion in the fetal heart rate response to sound, from reactive to nonreactive, 4 weeks prior to the delivery of stillborn infants. Read and Miller, 8 using a 2,000 Hz (I05 to I20 dB) stimulus observed that when the fetal heart rate acceleration evoked exceeded 15 bpm the subsequent contraction stress test was always negative and pregnancy outcome was good. Trudinger and Boylan 4 reported a greater discriminatory value for the acoustic stimulation test than for the nonstress test in detecting fetal compromise. The hypoactive, nonreactive fetuses who experienced a change to a reactive pattern upon application of sound had a good outcome, in the experience of Zugaib and Behle. 5
Test
No.
%
20/141 4/20
14.2 20.0
17/132 7/27
12.0 25.9
l/16 217
6.3 36.4
4/141 1/20
2.8 5.0
4/132 l/27
3.0 3.7
0/16 017
0 0
1 min Apgar score 0-6
Nonstress test Reactive Nonreactive Acoustic stimulation test Reactive Nonreactive Contraction stress test Negative Positive
5 min Apgar score 0-6
Nonstress test Reactive Nonreactive Acoustic stimulation test Reactive Nonreactive Contraction stress test Negative Positive
The results of the present study revealed a comparable incidence of spontaneous and sound-generated reactivity when tests were performed within 7 days of delivery. The occurrences of intrapartum distress, with the use of a strict definition of electronic distress (as set forth in Material and methods), were essentially the same in both reactive groups (12.8% and I2.9%) (Table IV). The incidence of meconium and the incidence of nonvigorous infants (Apgar scores of :56 at 5 minutes) were not significantly different when reactive nonstress tests and acoustic stimulation tests were compared and when nonreactive nonstress tests and acoustic stimulation tests were compared. These data demonstrate comparable predictive value of the reactive nonstress test and the reactive acoustic stimulation test with respect to the outcome measures evaluated. The results obtained are in agreement with the data reported by Trudinger and Boylan 4 and by Zugaib and Behle. 5 In summary, the acoustic stimulation test is a safe, rapid test of fetoplacental sufficiency that appears to perform comparably to the traditional nonstress test. We are continuing to correlate perinatal outcome with acoustic stimulation test results to be sure that acoustic stimulation test performance can withstand the scrutiny of thousands of patients. We wish to thank David Saar of Black and Decker Corporation for the sound pressure level measurements. REFERENCES 1. Keane, M. W. D., Horger, E. 0., and Vice, L.: Comparative study vf stressed and nonstressed antepartum fetal heart rate testing, Obstet. Gynecol. 57:320, 1981. 2. Druzin, M.D., Gratacos,J., and Paul, R. H.: Antepartum fetal heart rate testing. VI. Predictive reliability of "nor-
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3. 4. 5. 6. 7. 8. 9. 10. 11.
mal" tests in the prevention of antepartum death, AM.]. 0BSTET. GYNECOL. 137:746, 1980. Rayburn, W., Zuspan, F., Mootley, M.D., and Donaldson, M.: An alternative to antepartum fetal heart rate testing, AM.]. 0BSTET. GYNECOL. 138:223, 1980. Trudinger, B. J., and Boylan, P.: Antepartum fetal heart rate monitoring: Value of sound stimulation, Obstet. Gynecol. 55:265, 1980. Zugaib, M., and Behle, 1.: Antepartum stress test, in Fetal Monitoring, ed. 1, Sao Paulo, Brazil, 1981, Roca. Brown, R., and Patrick, J.: The nonstress test: How long is enough? AM.]. 0BSTET. GYNECOL. 141:646, 1981. Paul, R. H., and Miller, F. C.: Antepartum fetal heart rate monitoring, Clin. Obstet. Gynecol. 21:375, 1978. Read,]. A., and Miller, F. C.: Fetal heart rate acceleration in response to acoustic stimulation as a measure of fetal well-being, AM.j. 0BSTET. GYNECOL. 129:512, 1977. Henshall, W. R.: Intrauterine sound levels, AM. J. OBSTET. GYNECOL. 112:576, 1972. Walker, D., Grimwade, J., and Wood, C.: Intrauterine noise: A component of the fetal environment, AM. J. 0BSTET. GYNECOL. 109:91, 1971. Forbes, H. S., and Forbes, H. B.: Fetal sense reactions: Hearing,]. Comp. Psycho!. 7:353, 1927.
Antepartum FHR response to sound
12. Sontag, L. W., and Wallace, R. F.: Changes in the rate of the human fetal heart response to vibratory stimuli, Am. ]. Dis. Child. 51:583, 1936. 13. Sontag, L. W., and Bernard, J.: Fetal reactivity to tonal stimulation: A preliminary report, J. Gen. Psycho!. 70: 205, 1947. 14. Johansson, B., Wedenberg, E., and Westin, B.: Measurement of tone response by the human foetus, Acta Otolaryngol. 57:188, 1964. 15. Grimwade,J. C., Walker, D. W., Bartlett, M., Gordon, S., and Wood, C.: Human fetal heart rate change and movement in response to sound and vibration, AM. J. 0BSTET. GYNECOL. 109:86, 1971. 16. Murphy, K. P., and Smyth, C. N.: Response of fetus to auditory stimulation, Lancet 1:1972, 1962. 17. Slomka, C., and Phelan,]. P.: Pregnancy outcome in the patient with a nonreactive nonstress test and a positive contraction stress test, AM.]. OBSTET. GYNECOL. 139:11, 1981. 18. Keegan, K. A., and Paul, R. H.: Antepartum fetal heart rate testing. IV. The nonstress test as a primary approach, AM. j. 0BSTET. GYNECOL. 136:75, 1980.
Production of active and acid-activated renin by cultured explants of human fetal tissues A. Y. Warren, D. J. Craven, and E. M. Symonds Nottingham, England Various fetal tissues with gestational ages that ranged from 6 to 22 weeks were cultured as explants, and the culture media were examined for the production of both active and acid-activated renin. Media from cultures of fetal kidney, both the male and female genital tracts, and umbilical cord vessels were found to contain large quantities of active and acid-activated renin. Consistent differences in the production patterns of renin were found between the tissues, which may reflect the different potentials of the tissues to produce renin in vivo. (AM. J. 0BSTET. GYNECOL. 148:45, 1984.)
The discovery of high concentrations of renin in human amniotic fluid' prompted the investigation of the female genital tract as a possible site of renin synthesis. Myometrium and chorion laeve were found to contain and be capable of synthesizing large amounts of renin in vitro. 2 • :l It would appear, however, that uterine sources of renin may be more important at a local level, rather than in the general circulation, since renin activity levels reported in uterine venous plasma were not invariably elevated compared to peripheral levels. 4 Two forms of renin have been described-active From the Department of Obstetrics and Gynaecology, University Hospital, Queens Medical Centre. Received for publicaton February 11, 1983. Revised june 6, 1983. Accepted july 12, 1983. Reprint requests: Dr. E. M. Symonds, Department of Obstetrics and Gynaecology, University Hospital, Queens Medical Centre, Nottingham, NG7 2UH, England.
renin, which reacts with its substrate at a physiologic pH, and an acid-activated renin, inactive at a normal pH." Recent studies have implicated tissue kallikreins to be the physiologic activators of inactive renin, 6 thereby indicating that renin may function locally in specific tissues, producing angiotensin II close to its site of action. The presence of active and acid-activated renin in the human female genital tract and the production in vitro of both forms of renin by specific tissues' enhance the possibility of a local role for the renin-angiotensin system in the female genital tract. In this study, we investigated the potential synthesis of renin by various fetal tissues, in an attempt to assess the contribution of fetal renin to the maternal pool and the importance of fetal renin production in utero.
Material and methods Tissues were collected from six patients who underwent termination of pregnancy between 6 and 22
45