British Journal of Obstetrics and Gynaecology February 1975. Vol. 82. pp. 172-175
MATERNAL CARDIOMYOPATHY OF PREGNANCY CAUSING STILLBIRTH BY
R. J. RAND,Registrar Bradford Royal Infirmary
D. M. JENKINS, Senior Lecturer Department of Obstetrics and Gynaecology, University of Leeds AND
D. G. SCOTT,Lecturer Department of Immunology, Leeds General In$rmary Summary Cardiomyopathy of pregnancy developed in a healthy primigravida at 34 weeks gestation and was followed two weeks later by the spontaneous delivery of a fresh stillbirth. An immunological basis underlying both the mother’s condition and the fetal death was suggested by the presence of myocardial antibodies in maternal and cord blood. Reference is made to two other cases in which a similar pathological process may have occurred.
ALTHOUGH there have been many reported cases of cardiomyopathy of pregnancy and the
epistaxes requiring hospital admission on three occasions. However, the prothrombin and kaolin/cephalin times were normal ; the platelet count was 253,000 per cu. mm. with normal morphology; the differential white cell count was normal and the erythrocyte sedimentation rate was 92 mm. in the first hour. The blood urea and electrolytes were normal. Total serum protein levels were normal but plasma electrophoresis demonstrated raised levels of gamma globulin and reduced albumin. The fibrinogen degradation products concentration in peripheral blood was greater than 10 pg./ml. and therefore outside the normal range for early pregnancy. This abnormality persisted until after delivery. By 27 weeks her haemoglobin had fallen to 7.9 g./100 ml. despite haematinic therapy and was transfused with 3 litres of blood. At 29 weeks her blood pressure was recorded as 170/90 mm. Hg. She was therefore admitted to hospital where she remained until after delivery. However, the blood pressure quickly
puerperium since the disease was first described in 1849 (Meadows, 1960), and in spite of the recognition that over 80 per cent of premenopausal women developing cardiomyopathy do so in relation to pregnancy (Seftel and Susser, 1961; Stuart, 1968; Burch et al., 1971), there is still doubt about its precise nature but an immunological basis seems at least a possibility. On the evidence presented in our case report it appeared possible that immunological factors were operative in both the maternal cardiomyopathy and in the fresh stillbirth that occurred two weeks later. CASEREPORT The patient was a 27-year-old married primigravida with no personal or family history of heart disease or hypertension. She was prone to minor nose bleeds. From the 16th week of pregnancy onwards she had recurrent severe 172
CARDIOMYOPATHY OF PREGNANCY
settled to 140/90 mm. Hg or less and there was no associated albuminuria. Serial measurements of 24 hour urinary oestriol levels and of the fetal biparietal diameter by ultrasound were normal. At 34 weeks gestation acute heart failure developed with severe dyspnoea and oedema. There was a loud first heart sound and two distinct systolic murmurs, one of which was best heard at the apex and radiated to the axilla and the other of which was loudest down the right sternal edge and radiated to the clavicle. There was no pyrexia, chest pain, cough, or sign of deep vein thrombosis. An X-ray showed marked cardiomegaly with an elevated right hemidiaphragm and dilated upper pulmonary veins. There was no recent lung lesion, nor other cause for the enlarged heart. An electrocardiograph showed sinus tachycardia but was otherwise normal. The haemoglobin was 11.2 g./ 100 ml.; the white cell count was 6,900 cu. mm.; the blood film and platelets were normal; the erythrocyte sedimentation rate was 55 mm. in the first hour; and the blood urea and electrolytes were all normal apart from a slightly low serum potassium of 3 - 6 mEq./l. The serum albumin was 2. 4 g./100 ml. and total serum proteins were normal. As in early pregnancy plasma electrophoresis demonstrated normal levels of alpha- 1, alpha-2 and beta-globulins, but raised gammaglobulin, and reduced albumin. The 24-hour excretion of catecholamines was not elevated. Thyroid function was normal as assessed by the protein bound iodine, and triiodothyronine and tetraiodothyronine uptakes. Virus antibody titres against Myxovirus influenzae A and B, adenovirus, psittacosis virus, coxiella burnetti, Mycoplasma pneumoniae and Coxsackie viruses B1, B,, B,, B4,BB,and B6 were all low and they did not rise in the course of the following two weeks. Antimyocardial sarcolemma antibodies were detected in the peripheral blood in a titre of 1 in 45. Cardiomyopathy of pregnancy was diagnosed and treatment initiated with frusemide 40 mg. daily and potassium supplements. Within 24 hours 5 litres of urine were excreted and by the fifth day the cardiac failure had cleared. Two weeks later, at 36 weeks gestation, premature labour commenced. After two hours of regular contractions a vaginal examination
173
revealed the cervix was 7 cm. dilated. An amniotoiny was performed releasing thickly meconium stained liquor amnii. At the same time the fetal heart rate became irregular with severe bradycardia between contractions. Despite prompt delivery with the ventouse extractor, the baby, a boy weighing 2.32 kg., was stillborn. No physical disturbance followed the delivery. The patient was mobilized early and discharged at six days post partum. The serum potassium was 3.6 mEq./I. and serum albumin 2.2 g./lOO ml. Plasma electrophoresis showed normal gammaglobulin levels. Fibrinogen degradation products were still present in the peripheral blood. Six weeks later the patient was extremely well. The heart was no longer enlarged on screening and the electrocardiograph was normal. Morbid anatomy Autopsy of the baby showed no macroscopic abnormalities. Sections of the heart showed unusually eosinophillic and homogeneous myocardial cytoplasm; cytoplasmic outlines were irregular and blurred with complete loss of striations. Between the myocardial fibres there were wide spaces filled with faintly eosinophillic fluid. The myocardial nuclei, however, were preserved, and an inflammatory response was evident. The appearances were consistent with the influence of an antibody. Immunological studies The results of immunoglobulin estimations made at delivery are shown in Table I. The cord serum was positive in a titre of 1 in 15 for myocardial sarcolemma antibodies identical to those detected in the maternal blood. TABLE I Immunoglobulin levels at delivery and their normal range Type of Value at Normal immunodelivery range globulin (mg./100 ml.) (mg./lOO ml.) Cord blood
Maternal blood
IgG IgM
1150 13
1077-1839 8.2-23 ' 0
IG IgA
1900 640 125
300-1 600
IgM
14-20 50-200
174
RAND, JENKINS AND SCOTT
Sections of the heart and kidney were studied by direct immunofluorescence with fluorescein labelled antisera to human immunoglobulins, and indirectly with antisera to human complement. IgG was irregularly present throughout the heart, linearly distributed alongside scattered muscle fibres in the sarcolemma and adjacent connective tissue fibrils, and in the sarcoplasm of occasional myofibres. No IgA, IgM or complement was detected. No additional fixation of IgG was noted when sections were reacted with maternal serum prior to reaction with fluorescein labelled anti-IgG antisera, although the maternal serum was shown to contain immunoglobulins capable of fixing to the sarcolemma and subsarcolemmal sarcoplasm of rat heart. No renal immunohistological abnormality was noted. The patient and her husband were 0 Rhesus positive. The HL-A types of mother and husband were reported HL-A3, 12, W10 and HL-A1, 9, 8 respectively when tested against 20 antisera.
DISCUSSION The incidence of cardiomyopathy of pregnancy and the puerperium has been quoted as between 1 in 1300 and 1 in 4000 confinements (Meadows, 1957; Woolford, 1952; Seftel and Susser, 1961), accounting for up to 5 per cent of cardiac deaths in pregnancy (Gouley et al., 1937). However, many authors do not believe this is a specific cardiomyopathy, but that the strain of pregnancy precipitates failure in a previously damaged heart (Bashour and Winchell, 1954; Benchimol et al., 1959; Gilchrist, 1963; Robinson et al., 1970; Hudson, 1972). Superadded hypertension may be an important aetiological factor, and is said to occur in up to 30 per cent of cases (Pierce et al., 1963). It is interesting that this patient had a high erythrocyte sedimentation rate, circulating fibrinogen degradation products and raised gamma globulins four months before her acute illness. She subsequently developed mild pre-eclampsia and this may have precipitated the cardiac failure. The frequent severe epistaxes were unexplained but abnormal bleeding has been described with cardiomyopathy of pregnancy (Hull and Hafkesbring, 1937; Meadows, 1957). The studies on the baby’s heart indicate a primary pathology rather than terminal anoxic
or postmortem changes. It is possible that damage to both the maternal and fetal myocardium was caused by a common agent, such as a virus. Cases are reported in which mothers have had a viral infection a few days before labour, and the baby has subsequently died of myocarditis. In some cases virus has been isolated from the baby’s myocardium (Javett et al., 1956; Kibrick and Benirschke, 1956; Van Creveld and De Jager, 1956; Delaney and Fukunaga, 1958; Woodward et al., 1960; Doshi and Lodge, 1973). However, in our case the maternal serum antibody titres estimated during the third trimester gave no evidence of recent viral infection, and the cord blood immunoglobulin levels did not suggest intrauterine viraemia. Sanders (1963) drew attention to the striking similarity between chronic infectious myocarditis and a large group of unexplained myocardial diseases, and he discussed the possible role of autoimmunity in their development. Other authors have suggested that the production of myocardial antibodies and the histology of affected hearts indicate that cardiomyopathy of pregnancy and the puerperium may be a primary autoimmune disease (Becker and Taube, 1962; Hudson, 1972). However, heart antibodies are not invariably present in this condition (Hughes et al., 1970; Robinson et al., 1970), and they are found in patients with rheumatic fever, and following myocardial infarctions or cardiac surgery (Kaplan and Frangley, 1969). Indeed antibody formation has been described as “the common denominator in myocardial disease” (Editorial, 1962). Therefore, whether the high titre of antimyocardial sarcolemma antibodies in this patient was the primary cause of her illness or secondary to underlying disease is uncertain. Heart antibodies in cord blood have not to our knowledge been recorded. Nevertheless, if maternal blood contains such IgG antibodies they will cross the placental barrier and the fetus is likely to be affected. This mechanism could explain the intrauterine death and the subsequent histological and immunological findings. Most case reports of cardiomyopathy of pregnancy fail to mention whether or not the baby survived. However, one of 15 patients
CARDIOMYOPATHY OF PREGNANCY
described by Brown et al. (1967) was almost identical to ours. Having responded to treatment for her unexplained cardiac failure, she went into spontaneous labour and had a fresh stillbirth after the fetal heart had stopped without warning during the second stage. A similar immunological explanation could account for the autopsy finding of cardiomyopathy on a baby who died a few minutes after delivery by postmortem Caesarean section, the mother having died of cardiac failure attributed to cardiomyopathy developing for the first time during the third trimester of her second pregnancy. This mother had no history of overt heart disease but two years earlier her first baby had died in infancy of cardiomyopathy (Redman, 1974). It is possible that she had an underlying autoimmune cardiomyopathy from the time of her first pregnancy and that both infant deaths were due to passively acquired antibodies. Our findings suggestthat immunological factors may play a role in the pathogenesis of cardiomyopathy of pregnancy and that there may be a transplacental influence on the fetus. This would represent a situation analogous to neonatal myasthenia gravis, thyrotoxicosis, and thrombocytopenic purpura in which auto-antibodies transmitted across the placenta cause disease in the baby. The effect, if not fatal, may be transient, clearing in the weeks following birth (Scott, 1966). ACKNOWLEDGEMENTS We thank Professor J. S. Scott for advice, Dr. A. J. Barson for the histological study, and Mr. G. A. Craig for allowing us to study his patient and report these findings. REFERENCES Bashour, F., and Winchell, P. (1954): Annals of Internal Medicine, 40, 803. Becker, F. F., and Taube, M. (1962): New England Journal of Medicine, 266, 62.
175
Benchimol, A. B., Carneiro, R. D., and Schesinger, P. (1959): British Heart Journal, 21, 89. Brown, A. K., Doukas, N., Riding, W. D., and Wyne Jones, E. (1967): British Heart Journal, 29, 387. Burch, G. E., McDonald, C. D., and Walsh, J. J. (1971): American Heart Journal, 81, 186. Delaney, T. B., and Fukunaga, F. H. (1958): New England Journal of Medicine, 259, 234. Doshi, R., and Lodge, K. V. (1973): Archives of Disease in Childhood, 48, 431 Editorial (1962) : Journal of the American MedicaI Association, 181, 784. Gilchrist, A. R. (1963): British Medical Journal, 1, 209. Gouley, B. A., McMillan, T. M., and Bellet, S. (1937): American Journal of Medical Sciences, 194, 185. Hudson, R. E. B. (1972): Cardiomyopathy. Volume 4, No. 1 of Cardiovascular Clinics. Edited by G. E. Burch. F. A. Davis and Co., Philadelphia, p. 4. Hughes, R. A. C., Kapur, P., Sutton, G. C., and Honey, M. (1970): British Heart Journal, 32, 272. Hull, E., and Hafkesbring, E. (1937): New Orleans Medical and Surgical Journal, 89, 550. Javett, S. M., Heyman, S., Mundel, B., Pepler, W. J., Lurie, H. I., Gear, J., Maesroch, V., and Kirsch, A. (1956) : Journal of Paediatrics, 48, 1. Kaplan, M. H., and Frangley, J. D. (1969): American Journal of Cardiology, 24,459. Kibrick, S., and Benirschke, K. (1956): New England Journal of Medicine, 255, 883. Meadows, W. R. (1957): Circulation, 15, 903. Meadows, W. R. (1960): American Journal of Cardiology, 6, 788. Pierce, J. A., Price, B. O., and Joyce, J. W. (1963): Archives of Internal Medicine, 111, 651. Redman, T. F. (1974) : Personal communication. Robinson, J. A., Grieble, H. G., and Anderson, T. 0. (1970): Cardiovascular Research, 4, 14. Sanders, V. (1963): American Heart Journal, 66, 707. Scott, J . S. (1966): British Medical Journal, 1, 1 , 559. Seftel, H., and Susser, M. (1961): British Heart Journal, 23, 43. Stuart, K. L. (1968): Quarterly Journal of Medicine, 37, 463. Van Creveld, S., and de Jager, H. (1956): Annales paediatriae Fenniae, 187, 100. Woodward, T. E., McCrumb, F. R., Carey, T. N., and Togo, Y . (1960): Annals of Internal Medicine, 53, 1130. Woolford, R. M. (1952): Ohio State Medical Journal, 48, 924.
MATERNAL CARDIOMYOPATHY OF PREGNANCY CAUSING STILLBIRTH BY
R. J. RAND,Registrar Bradford Royal Infirmary
D. M. JENKINS, Senior Lecturer Department of Obstetrics and Gynaecology, University of Leeds AND
D. G. SCOTT,Lecturer Department of Immunology, Leeds General In$rmary Summary Cardiomyopathy of pregnancy developed in a healthy primigravida at 34 weeks gestation and was followed two weeks later by the spontaneous delivery of a fresh stillbirth. An immunological basis underlying both the mother’s condition and the fetal death was suggested by the presence of myocardial antibodies in maternal and cord blood. Reference is made to two other cases in which a similar pathological process may have occurred.
ALTHOUGH there have been many reported cases of cardiomyopathy of pregnancy and the
epistaxes requiring hospital admission on three occasions. However, the prothrombin and kaolin/cephalin times were normal ; the platelet count was 253,000 per cu. mm. with normal morphology; the differential white cell count was normal and the erythrocyte sedimentation rate was 92 mm. in the first hour. The blood urea and electrolytes were normal. Total serum protein levels were normal but plasma electrophoresis demonstrated raised levels of gamma globulin and reduced albumin. The fibrinogen degradation products concentration in peripheral blood was greater than 10 pg./ml. and therefore outside the normal range for early pregnancy. This abnormality persisted until after delivery. By 27 weeks her haemoglobin had fallen to 7.9 g./100 ml. despite haematinic therapy and was transfused with 3 litres of blood. At 29 weeks her blood pressure was recorded as 170/90 mm. Hg. She was therefore admitted to hospital where she remained until after delivery. However, the blood pressure quickly
puerperium since the disease was first described in 1849 (Meadows, 1960), and in spite of the recognition that over 80 per cent of premenopausal women developing cardiomyopathy do so in relation to pregnancy (Seftel and Susser, 1961; Stuart, 1968; Burch et al., 1971), there is still doubt about its precise nature but an immunological basis seems at least a possibility. On the evidence presented in our case report it appeared possible that immunological factors were operative in both the maternal cardiomyopathy and in the fresh stillbirth that occurred two weeks later. CASEREPORT The patient was a 27-year-old married primigravida with no personal or family history of heart disease or hypertension. She was prone to minor nose bleeds. From the 16th week of pregnancy onwards she had recurrent severe 172
CARDIOMYOPATHY OF PREGNANCY
settled to 140/90 mm. Hg or less and there was no associated albuminuria. Serial measurements of 24 hour urinary oestriol levels and of the fetal biparietal diameter by ultrasound were normal. At 34 weeks gestation acute heart failure developed with severe dyspnoea and oedema. There was a loud first heart sound and two distinct systolic murmurs, one of which was best heard at the apex and radiated to the axilla and the other of which was loudest down the right sternal edge and radiated to the clavicle. There was no pyrexia, chest pain, cough, or sign of deep vein thrombosis. An X-ray showed marked cardiomegaly with an elevated right hemidiaphragm and dilated upper pulmonary veins. There was no recent lung lesion, nor other cause for the enlarged heart. An electrocardiograph showed sinus tachycardia but was otherwise normal. The haemoglobin was 11.2 g./ 100 ml.; the white cell count was 6,900 cu. mm.; the blood film and platelets were normal; the erythrocyte sedimentation rate was 55 mm. in the first hour; and the blood urea and electrolytes were all normal apart from a slightly low serum potassium of 3 - 6 mEq./l. The serum albumin was 2. 4 g./100 ml. and total serum proteins were normal. As in early pregnancy plasma electrophoresis demonstrated normal levels of alpha- 1, alpha-2 and beta-globulins, but raised gammaglobulin, and reduced albumin. The 24-hour excretion of catecholamines was not elevated. Thyroid function was normal as assessed by the protein bound iodine, and triiodothyronine and tetraiodothyronine uptakes. Virus antibody titres against Myxovirus influenzae A and B, adenovirus, psittacosis virus, coxiella burnetti, Mycoplasma pneumoniae and Coxsackie viruses B1, B,, B,, B4,BB,and B6 were all low and they did not rise in the course of the following two weeks. Antimyocardial sarcolemma antibodies were detected in the peripheral blood in a titre of 1 in 45. Cardiomyopathy of pregnancy was diagnosed and treatment initiated with frusemide 40 mg. daily and potassium supplements. Within 24 hours 5 litres of urine were excreted and by the fifth day the cardiac failure had cleared. Two weeks later, at 36 weeks gestation, premature labour commenced. After two hours of regular contractions a vaginal examination
173
revealed the cervix was 7 cm. dilated. An amniotoiny was performed releasing thickly meconium stained liquor amnii. At the same time the fetal heart rate became irregular with severe bradycardia between contractions. Despite prompt delivery with the ventouse extractor, the baby, a boy weighing 2.32 kg., was stillborn. No physical disturbance followed the delivery. The patient was mobilized early and discharged at six days post partum. The serum potassium was 3.6 mEq./I. and serum albumin 2.2 g./lOO ml. Plasma electrophoresis showed normal gammaglobulin levels. Fibrinogen degradation products were still present in the peripheral blood. Six weeks later the patient was extremely well. The heart was no longer enlarged on screening and the electrocardiograph was normal. Morbid anatomy Autopsy of the baby showed no macroscopic abnormalities. Sections of the heart showed unusually eosinophillic and homogeneous myocardial cytoplasm; cytoplasmic outlines were irregular and blurred with complete loss of striations. Between the myocardial fibres there were wide spaces filled with faintly eosinophillic fluid. The myocardial nuclei, however, were preserved, and an inflammatory response was evident. The appearances were consistent with the influence of an antibody. Immunological studies The results of immunoglobulin estimations made at delivery are shown in Table I. The cord serum was positive in a titre of 1 in 15 for myocardial sarcolemma antibodies identical to those detected in the maternal blood. TABLE I Immunoglobulin levels at delivery and their normal range Type of Value at Normal immunodelivery range globulin (mg./100 ml.) (mg./lOO ml.) Cord blood
Maternal blood
IgG IgM
1150 13
1077-1839 8.2-23 ' 0
IG IgA
1900 640 125
300-1 600
IgM
14-20 50-200
174
RAND, JENKINS AND SCOTT
Sections of the heart and kidney were studied by direct immunofluorescence with fluorescein labelled antisera to human immunoglobulins, and indirectly with antisera to human complement. IgG was irregularly present throughout the heart, linearly distributed alongside scattered muscle fibres in the sarcolemma and adjacent connective tissue fibrils, and in the sarcoplasm of occasional myofibres. No IgA, IgM or complement was detected. No additional fixation of IgG was noted when sections were reacted with maternal serum prior to reaction with fluorescein labelled anti-IgG antisera, although the maternal serum was shown to contain immunoglobulins capable of fixing to the sarcolemma and subsarcolemmal sarcoplasm of rat heart. No renal immunohistological abnormality was noted. The patient and her husband were 0 Rhesus positive. The HL-A types of mother and husband were reported HL-A3, 12, W10 and HL-A1, 9, 8 respectively when tested against 20 antisera.
DISCUSSION The incidence of cardiomyopathy of pregnancy and the puerperium has been quoted as between 1 in 1300 and 1 in 4000 confinements (Meadows, 1957; Woolford, 1952; Seftel and Susser, 1961), accounting for up to 5 per cent of cardiac deaths in pregnancy (Gouley et al., 1937). However, many authors do not believe this is a specific cardiomyopathy, but that the strain of pregnancy precipitates failure in a previously damaged heart (Bashour and Winchell, 1954; Benchimol et al., 1959; Gilchrist, 1963; Robinson et al., 1970; Hudson, 1972). Superadded hypertension may be an important aetiological factor, and is said to occur in up to 30 per cent of cases (Pierce et al., 1963). It is interesting that this patient had a high erythrocyte sedimentation rate, circulating fibrinogen degradation products and raised gamma globulins four months before her acute illness. She subsequently developed mild pre-eclampsia and this may have precipitated the cardiac failure. The frequent severe epistaxes were unexplained but abnormal bleeding has been described with cardiomyopathy of pregnancy (Hull and Hafkesbring, 1937; Meadows, 1957). The studies on the baby’s heart indicate a primary pathology rather than terminal anoxic
or postmortem changes. It is possible that damage to both the maternal and fetal myocardium was caused by a common agent, such as a virus. Cases are reported in which mothers have had a viral infection a few days before labour, and the baby has subsequently died of myocarditis. In some cases virus has been isolated from the baby’s myocardium (Javett et al., 1956; Kibrick and Benirschke, 1956; Van Creveld and De Jager, 1956; Delaney and Fukunaga, 1958; Woodward et al., 1960; Doshi and Lodge, 1973). However, in our case the maternal serum antibody titres estimated during the third trimester gave no evidence of recent viral infection, and the cord blood immunoglobulin levels did not suggest intrauterine viraemia. Sanders (1963) drew attention to the striking similarity between chronic infectious myocarditis and a large group of unexplained myocardial diseases, and he discussed the possible role of autoimmunity in their development. Other authors have suggested that the production of myocardial antibodies and the histology of affected hearts indicate that cardiomyopathy of pregnancy and the puerperium may be a primary autoimmune disease (Becker and Taube, 1962; Hudson, 1972). However, heart antibodies are not invariably present in this condition (Hughes et al., 1970; Robinson et al., 1970), and they are found in patients with rheumatic fever, and following myocardial infarctions or cardiac surgery (Kaplan and Frangley, 1969). Indeed antibody formation has been described as “the common denominator in myocardial disease” (Editorial, 1962). Therefore, whether the high titre of antimyocardial sarcolemma antibodies in this patient was the primary cause of her illness or secondary to underlying disease is uncertain. Heart antibodies in cord blood have not to our knowledge been recorded. Nevertheless, if maternal blood contains such IgG antibodies they will cross the placental barrier and the fetus is likely to be affected. This mechanism could explain the intrauterine death and the subsequent histological and immunological findings. Most case reports of cardiomyopathy of pregnancy fail to mention whether or not the baby survived. However, one of 15 patients
CARDIOMYOPATHY OF PREGNANCY
described by Brown et al. (1967) was almost identical to ours. Having responded to treatment for her unexplained cardiac failure, she went into spontaneous labour and had a fresh stillbirth after the fetal heart had stopped without warning during the second stage. A similar immunological explanation could account for the autopsy finding of cardiomyopathy on a baby who died a few minutes after delivery by postmortem Caesarean section, the mother having died of cardiac failure attributed to cardiomyopathy developing for the first time during the third trimester of her second pregnancy. This mother had no history of overt heart disease but two years earlier her first baby had died in infancy of cardiomyopathy (Redman, 1974). It is possible that she had an underlying autoimmune cardiomyopathy from the time of her first pregnancy and that both infant deaths were due to passively acquired antibodies. Our findings suggestthat immunological factors may play a role in the pathogenesis of cardiomyopathy of pregnancy and that there may be a transplacental influence on the fetus. This would represent a situation analogous to neonatal myasthenia gravis, thyrotoxicosis, and thrombocytopenic purpura in which auto-antibodies transmitted across the placenta cause disease in the baby. The effect, if not fatal, may be transient, clearing in the weeks following birth (Scott, 1966). ACKNOWLEDGEMENTS We thank Professor J. S. Scott for advice, Dr. A. J. Barson for the histological study, and Mr. G. A. Craig for allowing us to study his patient and report these findings. REFERENCES Bashour, F., and Winchell, P. (1954): Annals of Internal Medicine, 40, 803. Becker, F. F., and Taube, M. (1962): New England Journal of Medicine, 266, 62.
175
Benchimol, A. B., Carneiro, R. D., and Schesinger, P. (1959): British Heart Journal, 21, 89. Brown, A. K., Doukas, N., Riding, W. D., and Wyne Jones, E. (1967): British Heart Journal, 29, 387. Burch, G. E., McDonald, C. D., and Walsh, J. J. (1971): American Heart Journal, 81, 186. Delaney, T. B., and Fukunaga, F. H. (1958): New England Journal of Medicine, 259, 234. Doshi, R., and Lodge, K. V. (1973): Archives of Disease in Childhood, 48, 431 Editorial (1962) : Journal of the American MedicaI Association, 181, 784. Gilchrist, A. R. (1963): British Medical Journal, 1, 209. Gouley, B. A., McMillan, T. M., and Bellet, S. (1937): American Journal of Medical Sciences, 194, 185. Hudson, R. E. B. (1972): Cardiomyopathy. Volume 4, No. 1 of Cardiovascular Clinics. Edited by G. E. Burch. F. A. Davis and Co., Philadelphia, p. 4. Hughes, R. A. C., Kapur, P., Sutton, G. C., and Honey, M. (1970): British Heart Journal, 32, 272. Hull, E., and Hafkesbring, E. (1937): New Orleans Medical and Surgical Journal, 89, 550. Javett, S. M., Heyman, S., Mundel, B., Pepler, W. J., Lurie, H. I., Gear, J., Maesroch, V., and Kirsch, A. (1956) : Journal of Paediatrics, 48, 1. Kaplan, M. H., and Frangley, J. D. (1969): American Journal of Cardiology, 24,459. Kibrick, S., and Benirschke, K. (1956): New England Journal of Medicine, 255, 883. Meadows, W. R. (1957): Circulation, 15, 903. Meadows, W. R. (1960): American Journal of Cardiology, 6, 788. Pierce, J. A., Price, B. O., and Joyce, J. W. (1963): Archives of Internal Medicine, 111, 651. Redman, T. F. (1974) : Personal communication. Robinson, J. A., Grieble, H. G., and Anderson, T. 0. (1970): Cardiovascular Research, 4, 14. Sanders, V. (1963): American Heart Journal, 66, 707. Scott, J . S. (1966): British Medical Journal, 1, 1 , 559. Seftel, H., and Susser, M. (1961): British Heart Journal, 23, 43. Stuart, K. L. (1968): Quarterly Journal of Medicine, 37, 463. Van Creveld, S., and de Jager, H. (1956): Annales paediatriae Fenniae, 187, 100. Woodward, T. E., McCrumb, F. R., Carey, T. N., and Togo, Y . (1960): Annals of Internal Medicine, 53, 1130. Woolford, R. M. (1952): Ohio State Medical Journal, 48, 924.
