PREMATURE CONTRACTION OF T H E DUCTUS A R T E R I O S U S : A CA U SE O F F O E T A L D E A T H A. E. BECKER*, M. J. BECKER AND C. A. WAGENVOORT Laboratory of Pathological Anatomy, Wilhelmina Gasthuis, University of Amsterdam, Netherlands
PLATES XC
AND
XCI
CARDIAC failure in utero is an infrequent cause of stillbirth (Becker, 1976). The anatomical conditions causing foetal heart failure are diverse, but have the common feature of causing an excessive burden on the right ventricle (Moller, Lynch and Edwards, 1966). Among these conditions premature closure of the ductus arteriosus, although exceedingly rare, should be included. The condition is defined as an obstructive narrowing prior to birth, which then prevents normal foetal circulation (Cassels, 1973). To our knowledge there are only five reported instances of premature closure of the ductus arteriosus (Chevers, 1847; Alexandrowsky, 1916; Fritz, 1940; Kohler, 1967; Arcilla, Thilenius and Ranniger, 1969). Four of these were either stillborn or died within a few hours after delivery. The fifth case has been presented by Arcilla et al. (1969) who made the unique observation of a newborn infant with signs of congestive cardiac failure proven by catheter studies to be caused by premature closure of the ductus. That case of neonatal cardiac failure was successfully treated by medical management. The present communication describes the necropsy findings in two cases of foetal heart failure in which in-utero obliteration of the ductus arteriosus was thought to play a major role. CASEREPORTS Case 1 A male infant, born at a gestational age of 39 wk after an uneventful pregnancy, was delivered spontaneously. During delivery an episode of bradycardia was noticed, with spontaneous return to normal rhythm. When the child was born the umbilical cord appeared to be twisted around his neck. At that time the infant again presented bradycardia and rapidly developed severe cyanosis, notwithstanding the fact that the umbilical cord was removed within seconds. The amniotic fluid appeared clear and showed no meconium contamination. The child died within minutes after the delivery, with signs of extreme asphyxia. The autopsy showed a term and fully mature baby boy with peripheral cyanosis. Multiple asphyxia1 haemorrhages were seen. The liver and spleen were congested weighing 200 and 15 g, respectively. The abdominal cavity contained 15 ml of clear fluid and there was slight Received 13 Feb. 1976; accepted 27 Apr. 1976.
* Address for correspondence : Dr A. E. Becker,Laboratoryof Pathological Anatomy, Wilhelmina
Gasthuis, Eerste Helmersstraat 104, Amsterdam, The Netherlands. J. PATH.-VOL.
121 (1977)
187
188
A. E. BECKER, M. J. MECKER AND C. A . WACENVOORT
subcutaneous oedema of the extremities. The heart was normally developed. The right atrium and the right ventricle were dilated. The floor of the fossa ovalis showed an outbulging towards the left atrium, albeit that the foramen ovale was normally developed and widely patent. There were no septal defects. The ductus arteriosus although still probe patent, was definitely narrowed, its maximal diameter being 2 mm (fig. 1). Histological sections of the ductus revealed a normal structure (fig. 1B) as usually encountered if contracted (Bakker, 1962), without structural abnormalities of the wall. The pulmonary arteries were of normal calibre. The average medial thickness, assessed from 50 muscular pulmonary arteries, was 21.9 per cent. The lungs were congested, poorly aerated and on microscopy showed diffuse intra-alveolar haemorrhages. The pulmonary veins were congested. The placenta weighed 300 g and was of normal size and structure; oedema was not observed. Case 2
A male infant was spontaneously born in the breech position after an uneventful pregnancy. During the delivery the child developed asphyxia and when born was in a critical condition. Resuscitation failed and the infant was declared dead within an hour after delivery. The autopsy showed a fully mature infant. There was peripheral cyanosis and slight subcutaneous oedema. There were multiple asphyxia1 haemorrhages. The lungs were poorly aerated and congested and on microscopic examination showed multiple intraalveolar and septal haemorrhages. The muscular pulmonary arteries were normal with an average thickness, determined in 50, of 20.9 per cent. Liver and spleen were markedly congested, weighing 195 and 17 g respectively. There was a slight increase in the amount of fluid in the abdominal cavity. The placenta was slightly oedematous, with a total weight of 505 g. The heart was normally developed. The right atrium showed a dilated cavity with bulging of the floor of the fossa ovalis. The foramen ovale was otherwise normally developed and patent. The only abnormality noted was a markedly narrowed ductus arteriosus, being patent to a probe with a maximal diameter of 2 mm (fig. 2). Histological sections revealed a ductal architecture suggestive of contraction as the cause of obliteration {fig. 2B).
DISCUSSION Each of these two stillborn infants presented at autopsy with definite signs of congestive heart failure. There was generalised oedema, ascites and enlargement of liver and spleen. Moreover, the placenta in case 2 showed marked oedema; hydramnios was not observed. The only anatomical alteration in these two cases that could explain the findings of congestive heart failure was a narrowed ductus arteriosus. The ductus plays an important role during foetal development in by-passing the non-functioning lungs (fig. 3). In the immediate postnatal period, at the time that the pulmonary circulation adjusts to postnatal circumstances, this role is still important. In this phase it remains patent and still may allow a right-to-left shunt, keeping pace with the alterations that occur in pulmonary vascular resistance (Adams and Lind, 1957). It follows that premature closure may have a serious effect on the foetal or neonatal circulation, leading to an excessive burden on the right ventricle (fig. 3). From these functional reasonings one may assume that the foetal ductus at autopsy is always widely patent. Wilson (1958), however, reported that among a series of 37 stillborn infants the ductus at autopsy was found to be contracted in three instances and partly contracted in another eight. He also
B ~ c K ~BK~ ,C K EAND H WAG~NVOOKT
PLATE XC
DUCTUS ARTtKlOSUS CONTRACTION
FIG.1.-Case 1. A, Rase of heart with normally positioned aorta (Ao) and pulmonary trunk (PT). The ductus arteriosus has been cross-sectioned. The external diameter has decreased, its wall appears thickened and the lumen is markedly narrowed. B, Microscopic study of the ductus arteriosus shows contraction, but no structural wall abnormalities. Haematoxylin and eosin (HE). x 16.
BECKER,BECKERA N D WACitNVOUKT
ARTFRIOSUS DUCTUS
FIG.?.-Case
PLATEXCI
CON1 RACTIOY
2. A, Superior view of the base of the heart showing the aorta (Ao) and pulmonary arteries (PA). The ductus arteriosus has been cross-sectioned, The wall appears thickened, due to contraction, with a slit-like lumen. B, Microscopic study of the ductus arteriosus reveals a contracted ductus, without structural abnormalities. HE. x 31.
DUCTUS ARTERIOSUS CONTRACTION
189
noted an interesting relationship between ductal contraction and prematurity of the infant. Both infants here reported, however, were mature. Wilson did not attribute any pathological significance to his observations, but merely regarded them as morphological evidence in the human for the theory that ductal obliteration starts off by contraction. Nevertheless his findings call for caution in attributing functional significance to a contracted ductus found at autopsy. We are convinced that the finding of a narrowed ductus arteriosus alone does not merit far-reaching conclusions but that the combination of ductal narrowing with signs of congestive heart failure is of importance.
I
circ:ulation
of D.A.
FIG.3.-Schematic drawing to illustrate the importance of the ductus arteriosus as a conduit for right ventricular blood to by-pass the hghly resistant pulmonary circulation. Premature closure results in a volume load of the right heart chambers such as to render the foramen ovale restrictive and may result in right-sided heart failure.
How then does premature closure of the ductus affect the circulation? If it occurs it would result in loss of the physiological pulmonary artery-to-aorta shunt and redirect this portion of the cardiac output either through the pulmonary vascular bed or to the systemic circulation via a septa1 defect for example through the foramen ovale. The foramen ovale in each of the two cases did indeed show evidence of increased right-to-left blood flow at that level. The valve of the foramen ovale was stretched and bulging into the left atrium. It can be concluded that the volume load on the right heart, in these circumstances, may become excessive, rendering a normal foramen ovale
190
A . E. BECKER, M. J. BECKER AND C. A . WAGENVOORT
restrictive to the increased volume of blood that is required to be moved through it (fig. 3). Premature closure of the ductus may, therefore, lead to right heart failure and consequently the pulmonary arteries should show evidence of resistance to an excessive pulmonary flow. Indeed, morphometric studies of muscular pulmonary arteries failed to indicate dilatation of these vessels in either case as would have been expected if the pulmonary vascular bed had adapted to accommodate excessive pulmonary flow. Their average medial thickness was within the upper normal limits for this age-group (Wagenvoort, Neufeld and Edwards, 1961). Dilatation of uninjected pulmonary arteries, if present, can be clearly demonstrated even in newborn infants (Dammann and Ferencz, 1956; Wagenvoort and Edwards, 1961). What then caused the ductus to behave inappropriately? So far there has been no conclusive explanation for this phenomenon. The only feature that both infants had in common was the fact that the delivery was accompanied by severe asphyxia. It has been shown experimentally (Born et al., 1956) that hypoxaemia may lead to ductal contraction. Whether this mechanism was operative in these two cases remains a matter for speculation, particularly since the physiology of normal postnatal closure of the ductus is still subject to disagreement (Cassels). Awareness of in-utero closure of the ductus arteriosus as a possible cause of foetal heart failure and foetal death perhaps may lead to the discovery of additional cases and to an improved understanding of the pertinent pathophysiology. SUMMARY Necropsy findings are presented of two cases of foetal heart failure secondary to premature, in-utero contraction of the ductus arteriosus. Premature ductal contraction should lead to a redirection of the right heart output either through the pulmonary vascular bed or to the systemic circulation via the foramen ovale. The muscular pulmonary arteries, however, were not dilated, indicating that no excessive pulmonary flow had occurred. The increased volume load on the right heart may have rendered the foramen ovale restrictive, with rightsided heart failure as a consequence. Premature closure of the ductus arteriosus should be considered a cause of foetal or early neonatal death. REFERENCES ADAMS,F. H., AND LIND, J. 1957. Physiologic studies on the cardiovascular status of normal newborn infants (with special reference to the ductus arteriosus). Pediatrics, 19, 431. ALEXANDROWSKY, A. 1916. Stenose des Ductus Arteriosus Botalli mit allgemeiner angeborener Wassersucht. Bed., 16, 80. ARCILLA,R. A., THILENIUS, 0. G., AND RANMGER,K. 1969. Congestive heart failure resulting from suspected ductal closure in-utero. J. Pediat., 75, 74. BAKKER,P. M. 1962. Morphogenese en involutie van de ductus arteriosus bij de mens. Thesis, Leiden. BECKER,M. J. 1976. Intra-uteriene vruchtdood. Een morphologische studie van 100 doodgeborenen. Thesis, Amsterdam.
DUCTUS ARTERIOSUS CONTRACTION
191
BORN,G. V. R., DAWES, G. S., MOTT,J. C., AND REMICK, B. R. 1956. The constriction of the ductus arteriosus caused by oxygen and by asphyxia in newborn lambs. J. Physiol. (London), 132,304. CASSELS, D. E. 1973. The ductus arteriosus. Charles C. Thomas, Springfield, p. 309. CHEVERS, N. 1847. Remarkable contraction of the ductus arteriosus in a newborn infant. Trans. Pathol. SOC.London, 1, 60. DAMMANN, J. F., AND FERENCZ, C. 1956. The significance of the pulmonary vascular bed in congenital heart disease. 111. Defects between the ventricles or great vessels in which both increased pressure and blood flow may act upon the lungs and in which there is a common ejectable force. Amer. Heart J., 52, 210. FRITZ,E. 1940. Foetaler Verschluss des Ductus Botalli. Deutsch. Z. Ges. Ger. Med., 32, 384. KOHLER, H. G. 1967. Intra-uterine closure of the ductus arteriosus. Abstract. Arch. Dis. Childh., 42, 335. MOLLER, J. H., LYNCH,R. P., AND EDWARDS, J. E. 1966. Fetal cardiac failure resulting from congenital anomalies of the heart. J . Pediat., 68, 699. WAGENVOORT, C. A., NEUFELD, H. N., AND EDWARDS, J. E. 1961. The structure of the pulmonary arterial tree in fetal and early postnatal life. Lab. Invest., 10, 751. WAGENVOORT, C. A., AND EDWARDS, J. E. 1961. The pulmonary arterial tree in pulmonic atresia. Arch. Path., 71, 646. WILSON,R. R. 1958. Post-mortem observations on contraction of the human ductus arteriosus. Br. Med. J., 1, 810.
Vol. 121, No. 2, February 1977 was issued on 17.2.77
PLATES XC
AND
XCI
CARDIAC failure in utero is an infrequent cause of stillbirth (Becker, 1976). The anatomical conditions causing foetal heart failure are diverse, but have the common feature of causing an excessive burden on the right ventricle (Moller, Lynch and Edwards, 1966). Among these conditions premature closure of the ductus arteriosus, although exceedingly rare, should be included. The condition is defined as an obstructive narrowing prior to birth, which then prevents normal foetal circulation (Cassels, 1973). To our knowledge there are only five reported instances of premature closure of the ductus arteriosus (Chevers, 1847; Alexandrowsky, 1916; Fritz, 1940; Kohler, 1967; Arcilla, Thilenius and Ranniger, 1969). Four of these were either stillborn or died within a few hours after delivery. The fifth case has been presented by Arcilla et al. (1969) who made the unique observation of a newborn infant with signs of congestive cardiac failure proven by catheter studies to be caused by premature closure of the ductus. That case of neonatal cardiac failure was successfully treated by medical management. The present communication describes the necropsy findings in two cases of foetal heart failure in which in-utero obliteration of the ductus arteriosus was thought to play a major role. CASEREPORTS Case 1 A male infant, born at a gestational age of 39 wk after an uneventful pregnancy, was delivered spontaneously. During delivery an episode of bradycardia was noticed, with spontaneous return to normal rhythm. When the child was born the umbilical cord appeared to be twisted around his neck. At that time the infant again presented bradycardia and rapidly developed severe cyanosis, notwithstanding the fact that the umbilical cord was removed within seconds. The amniotic fluid appeared clear and showed no meconium contamination. The child died within minutes after the delivery, with signs of extreme asphyxia. The autopsy showed a term and fully mature baby boy with peripheral cyanosis. Multiple asphyxia1 haemorrhages were seen. The liver and spleen were congested weighing 200 and 15 g, respectively. The abdominal cavity contained 15 ml of clear fluid and there was slight Received 13 Feb. 1976; accepted 27 Apr. 1976.
* Address for correspondence : Dr A. E. Becker,Laboratoryof Pathological Anatomy, Wilhelmina
Gasthuis, Eerste Helmersstraat 104, Amsterdam, The Netherlands. J. PATH.-VOL.
121 (1977)
187
188
A. E. BECKER, M. J. MECKER AND C. A . WACENVOORT
subcutaneous oedema of the extremities. The heart was normally developed. The right atrium and the right ventricle were dilated. The floor of the fossa ovalis showed an outbulging towards the left atrium, albeit that the foramen ovale was normally developed and widely patent. There were no septal defects. The ductus arteriosus although still probe patent, was definitely narrowed, its maximal diameter being 2 mm (fig. 1). Histological sections of the ductus revealed a normal structure (fig. 1B) as usually encountered if contracted (Bakker, 1962), without structural abnormalities of the wall. The pulmonary arteries were of normal calibre. The average medial thickness, assessed from 50 muscular pulmonary arteries, was 21.9 per cent. The lungs were congested, poorly aerated and on microscopy showed diffuse intra-alveolar haemorrhages. The pulmonary veins were congested. The placenta weighed 300 g and was of normal size and structure; oedema was not observed. Case 2
A male infant was spontaneously born in the breech position after an uneventful pregnancy. During the delivery the child developed asphyxia and when born was in a critical condition. Resuscitation failed and the infant was declared dead within an hour after delivery. The autopsy showed a fully mature infant. There was peripheral cyanosis and slight subcutaneous oedema. There were multiple asphyxia1 haemorrhages. The lungs were poorly aerated and congested and on microscopic examination showed multiple intraalveolar and septal haemorrhages. The muscular pulmonary arteries were normal with an average thickness, determined in 50, of 20.9 per cent. Liver and spleen were markedly congested, weighing 195 and 17 g respectively. There was a slight increase in the amount of fluid in the abdominal cavity. The placenta was slightly oedematous, with a total weight of 505 g. The heart was normally developed. The right atrium showed a dilated cavity with bulging of the floor of the fossa ovalis. The foramen ovale was otherwise normally developed and patent. The only abnormality noted was a markedly narrowed ductus arteriosus, being patent to a probe with a maximal diameter of 2 mm (fig. 2). Histological sections revealed a ductal architecture suggestive of contraction as the cause of obliteration {fig. 2B).
DISCUSSION Each of these two stillborn infants presented at autopsy with definite signs of congestive heart failure. There was generalised oedema, ascites and enlargement of liver and spleen. Moreover, the placenta in case 2 showed marked oedema; hydramnios was not observed. The only anatomical alteration in these two cases that could explain the findings of congestive heart failure was a narrowed ductus arteriosus. The ductus plays an important role during foetal development in by-passing the non-functioning lungs (fig. 3). In the immediate postnatal period, at the time that the pulmonary circulation adjusts to postnatal circumstances, this role is still important. In this phase it remains patent and still may allow a right-to-left shunt, keeping pace with the alterations that occur in pulmonary vascular resistance (Adams and Lind, 1957). It follows that premature closure may have a serious effect on the foetal or neonatal circulation, leading to an excessive burden on the right ventricle (fig. 3). From these functional reasonings one may assume that the foetal ductus at autopsy is always widely patent. Wilson (1958), however, reported that among a series of 37 stillborn infants the ductus at autopsy was found to be contracted in three instances and partly contracted in another eight. He also
B ~ c K ~BK~ ,C K EAND H WAG~NVOOKT
PLATE XC
DUCTUS ARTtKlOSUS CONTRACTION
FIG.1.-Case 1. A, Rase of heart with normally positioned aorta (Ao) and pulmonary trunk (PT). The ductus arteriosus has been cross-sectioned. The external diameter has decreased, its wall appears thickened and the lumen is markedly narrowed. B, Microscopic study of the ductus arteriosus shows contraction, but no structural wall abnormalities. Haematoxylin and eosin (HE). x 16.
BECKER,BECKERA N D WACitNVOUKT
ARTFRIOSUS DUCTUS
FIG.?.-Case
PLATEXCI
CON1 RACTIOY
2. A, Superior view of the base of the heart showing the aorta (Ao) and pulmonary arteries (PA). The ductus arteriosus has been cross-sectioned, The wall appears thickened, due to contraction, with a slit-like lumen. B, Microscopic study of the ductus arteriosus reveals a contracted ductus, without structural abnormalities. HE. x 31.
DUCTUS ARTERIOSUS CONTRACTION
189
noted an interesting relationship between ductal contraction and prematurity of the infant. Both infants here reported, however, were mature. Wilson did not attribute any pathological significance to his observations, but merely regarded them as morphological evidence in the human for the theory that ductal obliteration starts off by contraction. Nevertheless his findings call for caution in attributing functional significance to a contracted ductus found at autopsy. We are convinced that the finding of a narrowed ductus arteriosus alone does not merit far-reaching conclusions but that the combination of ductal narrowing with signs of congestive heart failure is of importance.
I
circ:ulation
of D.A.
FIG.3.-Schematic drawing to illustrate the importance of the ductus arteriosus as a conduit for right ventricular blood to by-pass the hghly resistant pulmonary circulation. Premature closure results in a volume load of the right heart chambers such as to render the foramen ovale restrictive and may result in right-sided heart failure.
How then does premature closure of the ductus affect the circulation? If it occurs it would result in loss of the physiological pulmonary artery-to-aorta shunt and redirect this portion of the cardiac output either through the pulmonary vascular bed or to the systemic circulation via a septa1 defect for example through the foramen ovale. The foramen ovale in each of the two cases did indeed show evidence of increased right-to-left blood flow at that level. The valve of the foramen ovale was stretched and bulging into the left atrium. It can be concluded that the volume load on the right heart, in these circumstances, may become excessive, rendering a normal foramen ovale
190
A . E. BECKER, M. J. BECKER AND C. A . WAGENVOORT
restrictive to the increased volume of blood that is required to be moved through it (fig. 3). Premature closure of the ductus may, therefore, lead to right heart failure and consequently the pulmonary arteries should show evidence of resistance to an excessive pulmonary flow. Indeed, morphometric studies of muscular pulmonary arteries failed to indicate dilatation of these vessels in either case as would have been expected if the pulmonary vascular bed had adapted to accommodate excessive pulmonary flow. Their average medial thickness was within the upper normal limits for this age-group (Wagenvoort, Neufeld and Edwards, 1961). Dilatation of uninjected pulmonary arteries, if present, can be clearly demonstrated even in newborn infants (Dammann and Ferencz, 1956; Wagenvoort and Edwards, 1961). What then caused the ductus to behave inappropriately? So far there has been no conclusive explanation for this phenomenon. The only feature that both infants had in common was the fact that the delivery was accompanied by severe asphyxia. It has been shown experimentally (Born et al., 1956) that hypoxaemia may lead to ductal contraction. Whether this mechanism was operative in these two cases remains a matter for speculation, particularly since the physiology of normal postnatal closure of the ductus is still subject to disagreement (Cassels). Awareness of in-utero closure of the ductus arteriosus as a possible cause of foetal heart failure and foetal death perhaps may lead to the discovery of additional cases and to an improved understanding of the pertinent pathophysiology. SUMMARY Necropsy findings are presented of two cases of foetal heart failure secondary to premature, in-utero contraction of the ductus arteriosus. Premature ductal contraction should lead to a redirection of the right heart output either through the pulmonary vascular bed or to the systemic circulation via the foramen ovale. The muscular pulmonary arteries, however, were not dilated, indicating that no excessive pulmonary flow had occurred. The increased volume load on the right heart may have rendered the foramen ovale restrictive, with rightsided heart failure as a consequence. Premature closure of the ductus arteriosus should be considered a cause of foetal or early neonatal death. REFERENCES ADAMS,F. H., AND LIND, J. 1957. Physiologic studies on the cardiovascular status of normal newborn infants (with special reference to the ductus arteriosus). Pediatrics, 19, 431. ALEXANDROWSKY, A. 1916. Stenose des Ductus Arteriosus Botalli mit allgemeiner angeborener Wassersucht. Bed., 16, 80. ARCILLA,R. A., THILENIUS, 0. G., AND RANMGER,K. 1969. Congestive heart failure resulting from suspected ductal closure in-utero. J. Pediat., 75, 74. BAKKER,P. M. 1962. Morphogenese en involutie van de ductus arteriosus bij de mens. Thesis, Leiden. BECKER,M. J. 1976. Intra-uteriene vruchtdood. Een morphologische studie van 100 doodgeborenen. Thesis, Amsterdam.
DUCTUS ARTERIOSUS CONTRACTION
191
BORN,G. V. R., DAWES, G. S., MOTT,J. C., AND REMICK, B. R. 1956. The constriction of the ductus arteriosus caused by oxygen and by asphyxia in newborn lambs. J. Physiol. (London), 132,304. CASSELS, D. E. 1973. The ductus arteriosus. Charles C. Thomas, Springfield, p. 309. CHEVERS, N. 1847. Remarkable contraction of the ductus arteriosus in a newborn infant. Trans. Pathol. SOC.London, 1, 60. DAMMANN, J. F., AND FERENCZ, C. 1956. The significance of the pulmonary vascular bed in congenital heart disease. 111. Defects between the ventricles or great vessels in which both increased pressure and blood flow may act upon the lungs and in which there is a common ejectable force. Amer. Heart J., 52, 210. FRITZ,E. 1940. Foetaler Verschluss des Ductus Botalli. Deutsch. Z. Ges. Ger. Med., 32, 384. KOHLER, H. G. 1967. Intra-uterine closure of the ductus arteriosus. Abstract. Arch. Dis. Childh., 42, 335. MOLLER, J. H., LYNCH,R. P., AND EDWARDS, J. E. 1966. Fetal cardiac failure resulting from congenital anomalies of the heart. J . Pediat., 68, 699. WAGENVOORT, C. A., NEUFELD, H. N., AND EDWARDS, J. E. 1961. The structure of the pulmonary arterial tree in fetal and early postnatal life. Lab. Invest., 10, 751. WAGENVOORT, C. A., AND EDWARDS, J. E. 1961. The pulmonary arterial tree in pulmonic atresia. Arch. Path., 71, 646. WILSON,R. R. 1958. Post-mortem observations on contraction of the human ductus arteriosus. Br. Med. J., 1, 810.
Vol. 121, No. 2, February 1977 was issued on 17.2.77
![[Premature constriction of the ductus arteriosus].](/assets/img/hold.png)
