Production of Fetal Asphyxia by Maternal Psychological Stress RONALD E. MYExaS
Laboratory of Perinatal Physiology, National Institute of Neurological Diseases and Stroke, National Institutes of Health, United States Public Health Service, Department of Health, Education, and Welfare, Bethesda, Maryland
THE mEA THAT EMOTIONALstress of the pregnant woman may affect the state of the fetus has been gaining acceptance based upon a mounting array of evidence. First, the maternal emotional state may influence the fetus in subtle and benign ways. The best known studies which show effects are those of Sontag and collaborators (1969) who demonstrated that a variety of influences which affect the mother including stress stimulation, exposure to music, and adverse home situations may alter the rate of the fetal heart and increase fetal movement. Copher and Huber (1967) have also demonstrated that stress stimulation of the mother can produce fetal heart rate changes with a short latency. Other studies have established that the fetal weight may be affected by maternal stress during pregnancy. Growth retarded fetuses originate in higher proportion among women of lower socioeconomic groups (e.g., Pachauri and Marwak, 1970). Women in other groups which undergo extraordinary stress during pregnancy (teenage or illegitimate pregnancies, pregnancies associated with absence of the father due to family breakdown, death, etc.), give use to higher incidences of growth retarded fetuses. Times of national catastrophe cause increased infertility and fetal loss and decreased infant birth weight (see Antonov, 1947). Still other data Reprinted with permission from Progress in EPH-Cestosis. Fortschritte in der EPH-Gestose-Forschung. 6. Meeting Organisation Gestosis, III. International Symposium EPH-Gestosis, Glasgow 26-29 September, 1973. E. T. Rippmann, CH-Basel; H. Stamm, CH-Baden; H. P. McEwan, GB-Glasgow;P. Howie, GB-Glasgow (eds.). Organisation Gestosis-Press 1975. This paper receivedthe Pavlovian Award in 1975. 51
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suggest a direct relation between the presence of maternal anxiety during pregnancy and impaired fetal growth (see Shaw, et al., 1970, and Sontag, 1940). More significant are studies which show that maternal psychologic stress during pregnancy cause a higher incidence of pregnancy abnormalities and fetal death, complications of the birth process, and disturbance of the status of the newborn (e.g., the investigations Of Davids and De Vault, 1962). The habitual aborter typifies such a circumstance. The habitual aborter is a woman who has demonstrated an inability to bear living young or who suffers a long sequence of stillbirths. The tendency for such habitual abortion seems in most instances to be associated with a specific personality make-up of the mother, viz., a tendency toward excessive anxiety and overreaction to life situations (e.g., the discussion of Grimm, 1962). Several large patient series have further shown that psychologic support of habitual aborters throughout their pregnancies greatly increases their ability to sustain the pregnancies and to give birth to live young (James 1963, Tupper and Weil, 1962, and Mann, 1959). The circumstance of habitual abortion emphasizes a correlation between maternal mind state and pregnancy outcome in terms of infant survival. It also shows that maternal mind state in some instances, at least, may exert effects on the fetus which are not benign or medically trivial but malignant and leading to fetal death. Thus, both epidemiologic and investigative studies of the human have shown a relation between maternal mind (emotional) state and the state of the fetus. Similar evidence is available with respect to rhesus monkey. The mean birth weight of rhesus monkey babies born to mothers held in captivity is significantly less than the mean birth weight of infants born to mothers living in a free-ranging environment ( Myers, 1972). Life in the particular controlled free-ranging setting is assumed to be less harassing for the pregnant animal than is her confinement during pregnancy in a single cage within a breeding colony where the animal suffers a daily contact with its human caretakers. It is also true that statistics gathered with respect to various rhesus monkey groups indicate differences in stillbirth incidence. The stillbirth incidence among females in a free-ranging colony is less than 5 per cent. In contrast, the stillbirth rate among monkeys confined to single cages varies from 14 to 17 per cent (e.g., Valeiro, et al., 1969) at least a threefold increase over that of the free-ranging setting. Finally, pregnant monkeys, captured from the wild in India; created and shipped by air to the United States; and required in the process to adjust to dramatically changed circum-
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stances exhibit a stillbirth rate which varies from 60 to nearly 100 per cent. These epidemiologic observations suggest that psychologic stress of pregnant rhesus monkey can cause adverse effects on the fetus. Other than the work of Sontag and of Cophler and Huber, direct evidence of an effect of psychological stress of the mother upon the fetus is lacking. However, during extensive physiologic studies on the pregnant rhesus monkey and fetus, observations have come to light which show a major effect of episodes of maternal psychological stress upon the fetal state of oxygenation and the fetal vital signs. Indeed, this effect can be shown to operate on a moment-by-moment basis. As the pregnant rhesus monkey comes out of barbiturate anesthesia following the surgical placement of maternal and fetal arterial TI[IqM FI['I~J6 1898 CHANGE3IN pO.z,~.ga pCOz IN ~ AS ~T).~R COid($ GIJT~/I/~10 IS I ~ INITIATI~I INTO PI[NTOSkq~I"AL ANI[SII~SIA
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FIc. 1. Blood chemical changes appearing in the fetus as the mother escapes from pentobarbital anesthesia. The impaired respiratory gas exchange (asphyxia) of the fetus regularly appears under these circumstances and is interpreted as due to the stress of the prior surgery and the increasing reactivity of the awakening mother, both of which cause an increased sympathotonia.
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catheters, the fetus in most instances develops blood chemical evidences of asphyxia. Figure 1 shows the progressive decline in the fetal blood pH and Po.~ and the increase in the fetal blood Pco~ as the mother emerges from pentobarbital anesthesia. These changes we believe to be due to increases in maternal sympathetic stimulation and adrenal medullary catecholamine release which occur as the mother emerges from anesthesia and becomes increasingly aware of her compromised state (held in a restraining chair in an unfamiliar environment, etc. ). The increased sympathotonia and catecholamine release causes vasoconstriction within the maternal abdominal visceral circulation and shunting of blood flow to other organs: particularly, the heart, the brain, and voluntary muscle. The gravid uterus, as one of .the visceral organs produced by the stress state. Intervillous space perfusion is impaired and asphyxia of the fetus develops. It could be suggested that the fetal asphyxia develops because of the trauma of surgery, the mechanical handling and possible damage of the uterus: because of altered blood supply produced by exposure to air; loss of amniotic fluid, etc. However, Figure 2 depicts the effects of pentobarbital administration to the mother (30 mg/kg) at a time when the mother had fully awakened and the fetus had shown asphyxia of such a degree as to portend an approaching fetal death. The reinstitution of anesthesia caused a dramatic reversal of the fetal asphyxia, the abnormal blood chemical values all being restored towards normality, e.g., note the increase in the Po._,, the decrease in the Pco._,, and the increase in the pH. This dramatic effect of reinstitution of anesthesia has appeared in every instance examined ( 8 cases out of 8). The regular improvement in respiratory gas state of the fetus on reinstitution of anesthesia of the mother clearly indicates that the asphyxia of the fetus did not arise in the first place due to any mechanical trauma or to any altered blood supply because of the surgery itself. Rather, the recovery seems to be due to the anesthetic's effect in interrupting the autonomic and other reflex pathways involved in the maternal response to stress. While observing the cardiovascular and blood chemical states of the mother and the fetus when the mother was fully awake and sitting in a restraining chair, a variety of phenomena were observed which provided direct evidence of a profound effect of maternal psychological stress on the fetus. One such example appears in the polygraph recording of Figure 3. The awake mother is sitting in a restraining chair in a darkened and quiet experimental room. The experimenter was absent for over an hour and returned to find an impaired recording of the maternal arterial blood pressure. The
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Fic. 2. Reinstitution of anesthesia by the IV injection of pentobarbital (35 mg/kg) regularly halts the asphyxial deterioration of the fetus and brings about a considerable repair of its state. These latter ameliorative effects appear independently of the alterations produced in the activity of the myometrium.
arterial catheter of the mother was immediately flushed with 0.5 cc of heparinized saline and the chair readjusted to take any possible tension off the catheter. The experimenter returned to the polygraph to find that these manipulations of the mother had led to major alterations in the fetal vital signs, the fetal heart rate having decreased from 195 to 110 beats/minute. Following this depression, the fetal heart rate gradually recovered to its previous value as the mother
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Fic. 3. Fetal heart rate and blood pressure changes produced by the experimenter's sudden return to the experimental room, the flushing of the maternal catheter, and the adjustment of the restraining chair. The experimenter's continued presence led to a prolonged restlessness and anxiety of the mother. Note the development of severe fetal bradycardia which required more than a half-hour for recovery. A fetal blood sample taken following recovery slill showed a moderate asphyxia of the fetus.
shifted around nervously in her chair and appeared anxious. Five other examples of fetal bradyeardia induced by the sudden return of the experimenter to the observation room following his prolonged absence have been recorded. In two instances, no flushing of either the maternal or the fetal catheters was carried out indicating that the vital signs changes in the fetuses were not caused by the flushing of one or the other of the catheters. In some instances, only a very minor stress to the mother could lead to definite vital signs changes in the fetus. Figure 4 depicts such an episode. Following the mother's recovery from anesthesia, the experimenter, aware that the mother had been food and water
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Fx6. 4. An episodeof mild fetal bradycardia and hypotensionproduced by the offeringof apple slicesto the mother. The mother averted her head and refused the slices. Again,the bradycardic episode developedon a background of an already establishedmoderate fetal asphyxia (see blood values).
deprived for almost 24 hours, approached and offered her several slices of apple. During the 3 minutes encounter, the mother averted her head and refused the food. On returning to the polygraph, the experimenter noted a readily apparent decrease both in the fetal heart rate and the blood pressure. These vital signs changes clearly developed in relation to the episode just described. Again, after removal of the stress, the fetal vital signs returned to their pro-stress levels. Superimposed upon the background values of the fetal vital signs in this and the preceding recording appear many late decelerations of the fetal heart rate (type II dips) each late deceleration
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associated with decreases in fetal mean blood pressure. These fetal vital signs changes occur in response to uterine contractions and reflect episodic alterations in fetal oxygenation. These and other episodes of unintended stressful stimulation of the mother have led to changes in fetal vital signs. These findings have suggested that psychologic stress stimulation the mother may aggravate an already existent fetal asphyxia due to escape from anesthesia (see above) and explain the episodes of fetal bradycardia and hypotension. To test this interpretation, 5 fully awake mothers were intentionally subiected to specific, well-defined episodes of psychologic stress stimulation. These episodes varied in duration from 1 to 2g minutes and consisted of the experimenter suddenly confronting the mother (in her chair), making loud noises, patting
FIc. 5. Three episodes of discrete psychological stress stimulation of mother 906F. On a signal, the bright room lights were turned on and the experimenter stepped in front of the mother stressing her by shouting at her, patting her on the head or shoulders, and clapping the hands. At the end of the 1-minute stimulation, the experimenter doused the lights and withdrew. Each such stimulation caused an episode of fetal bradycardia and hypotension. These vital signs changes of the fetus regularly began with a latency period of 50 seconds after the beginning of stress stimulation of the mother. The 3rd stress episode caused only a mild response, Note the presence of slight late decelerations of the fetal heart rate throughout the recording.
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her on the head and generally behaving in a threatening fashion. In no instance was the mother harmed in any way. Six episodes of such contrived of intended psychologic stress were applied to mother 906F. In every instance (as seen from the recordings of Figs. 5 and 6) such isolated stress stimulation led to an isolated episode of fetal bradycardia and hypotension. The first period of stress (depicted in Fig. 5) caused a decrease in the fetal heart rate from 165 to 95 beats/minute and a decrease in the mean fetal blood pressure from 49 to 33 mm Hg. The fetal vital signs responses, to the contrived maternal stress stimulations were clearly definable in 5 and still apparent in the 6th example. Fig. 6 depicts the slight but definite alterations in the fetal vital signs which appeared in response to a brief incoming telephone call. Of particular interest is the final episode of contrived stimulation of mother 906F as depicted in Fig. 6. This stimulation lasted 2~ minutes and produced profound changes in the fetal vital signs. The severity of the depressions of the fetal vital signs was such that it seemed possible that the fetus would fail to recover. However, the fetus of mother 906F did recover and was subsequently surgically delivered. This fetus, like the fetuses of other mothers awake in restraining chairs, suffered from a steady-state severe asphyxia and,
FIc. 6. Three further episodes of contrived psychological stress stimulation of mother 906F. Note the severity of the fetal response to the lest stress stimulation which lasted 2~I minutes. Fetal heart rate decreases to 70 beats/ minute and mean blood pressure falls to 26 mm Hg imply a near total lack of oxygen in the fetus. Should this circumstance have lasted more than several minutes, the fetus would not have survived.
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as a result, the recordings depicted in Figs. 5 and 6 also show typical late decelerations of the fetal heart rate in response to normal uterine contractions. Thus far it has been assumed that the vital signs changes of the fetuses observed in the preceding figures produced by the episodes of maternal psychologic stress stimulation were caused by episodes of enhanced fetal asphyxia. That this was indeed the case has been demonstrated by taking fetal blood samples just before, during, and after recovery from episodes of fetal bradycardia and hypotension caused by stress stimulation of the mother. Figure 7 illustrates one of four instances where such samples were taken in the present study. During the period of induced bradycardia and hypotension, the fetus showed significant decreases in arterial oxygenation; increases in arterial blood Pco2, and decreases in blood pH. The findings in TERM FETUS 1822 (2OH) JAN 21,1972 3 ~ PM (Unonesthetized) MATERNAL PSYCHIC STRESS EFFECTS ON FETUS. (25rain.recording) 200 MBP (mmHg)
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FIG. 7. Example of fetal blood sampling just before, during, and after the vital signs response of a fetus to a 1-minute psychologic stress stimulation of the mother. Note the decrease in Po2 and pH, and the increase in pCO., of the fetal arterial blood. Note also the restoration of the respiratory gas and pH values towards their pre-stress levels after recovery.
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all cases confirm the impression that the alterations in fetal vital signs produced by acute maternal stress stimulation are due to shortlived exacerbations of an already existent asphyxia. These findings provide direct evidence that maternal psychological stress may cause asphyxia of the fetus in the rhesus monkey.
Summary Several lines of evidence indicate that maternal psychological stress leads to adverse pregnancy outcome in rhesus monkey. Chronic anxiety causes an increased stillbirth rate, fetal growth retardation, and altered placental morphology. On another time scale, lightening of maternal anesthesia during surgery produces an impaired fetal oxygenation while re-institution of anesthesia ameliorates the fetal asphyxia. The present study, for the first time, demonstrates a relationship between specific episodes of maternal psychological' stress and exacerbation of fetal asphyxia in utero. Eight term pregnant rhesus monkeys were anesthetized with sodium pentobarbital. Catheters were placed both into the maternal and the fetal femoral arteries for the continuous recording of blood pressure and heart rate and for the intermittent campling of maternal and fetal blood. An open-ended catheter recorded intrauterine pressures. Following a complete repair, the anesthesia of the mothers was allowed to lighten. As the mothers awakened, the fetuses invariably showed the development of fetal asphyxia. A fetal acidosis developed and the fetal oxygenation and repair of acidosis. Studies while the mothers were fully awake showed the repeated and regular development of episodes of heightened fetal asphyxia produced by episodes of stressful stimulation of the mothers. Episodes of maternal psychological stress led to changes in both fetal vital signs and blood chemical findings. These alterations in fetal state regularly followed the onset of the episodes of psychological stress by 50 seconds. These changes also usually remitted 50 seconds following the termination of the periods of stress. These results demonstrated a direct and unequivocal relationship between maternal psychological stress and fetal asphyxia. It is assumed the maternal stress produces impairments in the circulation to the uterus through an increased sympathetic nervous system activity and a shunting of the maternal blood-flow from the abdominal viscera to other organs as occurs in the fight-orflight reaction. References Antonov, A. N.: Childrenborn during the siege of Leningrad in 1942. J. Ped. 30:250-259, 1947.
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Copher, D. E., and Huber, C. P.: Heart rate response of the human fetus to induced maternal hypoxia. Amer. I. Obstet. Gynec. 98:320-335, 1967. Davids, A., and De Vault, S.: Maternal anxiety during pregnancy and childbirth abnormalities. Psychosom. Med. 24:464-470, 1962. Grimm, E. tL: Psychological Investigation of habitual abortion. Psychsom. Med. 24:369-378, 1962. James, W. H.: The problem of spontaneous abortion. X. The efficacy of psychotherapy. Amer. I. Obstet. Gynec. 85:38-40, 1963. Mann, E. C.: Habitual abortion: A report, in 2 parts on 160 patients. Amer. I. Obstet. Gynec. 77:706-718, 1959. Myers, R. E.: The pathology of the rhesus monkey placenta. Acta Endocrin. Suppl. 166:221-257, 1972. Pachauri, S., and Marwak, S. M.: Socio-economic factors in relation to birth weight, lndian Ped. 7:462-468, 1970. Shaw, J. A., Wheeler, P., and Morgan, D. N.: Mother-infant relationship and weight gain in the first month of life. I. Am. Acad. Child Psychiat. 9:428444, 1970. Sontag, L. W.: Effect of fetal activity on the nutritional state of the infant at birth. Am. 1. Dis. Child. 60:621-630, 1940. Sontag, L. W., Steele, W. G., and Lewis, M.: The fetal and maternal cardiac response to environmental stress. Human Develop. 12:1-9, 1969. Tupper. C., and Weft, R. J.: The problem of spontaneous abortion. IX. The treatment of habitual aborters by pschotherapy. Am. 1. Obstet. Gynec. 83:421-424, 1962. Valerio, D. A., Miller, R. L., Innes, J. R. M., Courtney, K. D., Palotta, A. J., and Guttmacher, R. M.: Macaca Mulatta: The management of a laboratory breeding colony. New York, Academic Press, 1969, pp. 1-140.
