PLACENTAL EMBOLISM : A POSSIBLE CAUSE OF CEREBRAL DAMAGE IN THE NEWBORN
Philip B.James Ph.D., F.F.O.M. Wolfson Hyperbaric Medicine Unit Ninewells Medical School, Dundee DD1 9SY.
Summary: Many cases of cerebral damage in the newborn are unexplained and are not accounted for by the global hypoxia associated with neonatal asphyxia. Amniotic fluid embolism is an established cause of maternal morbidity where particulate debris from the placenta is responsible for the damage to the pulmonary capillary endothelium. The developing respiratory distress leads to pulmonary edema, with protein exudate and hyaline membrane formation. The microemboli may escape pulmonary entrappment and cause cerebral damage. Placental debris may also embolise the fetus and as the protection afforded by pulmonary filtration is not present until the adult circulation has been established, emboli may also cause cerebral damage in the neonate.
The middle cerebral artery is a preferred pathway for emboli and damage to the areas of the internal capsules may be associated with the later development of cerebral palsy. Introduction: In view of the complexity of events in the adaptation of the fetus to air breathing, it is not surprising that respiratory problems are an important cause of morbidity in the newborn. It is possible that several mechanisms may cause the respiratory distress syndrome (R.D.S.), in neonates and share the same clinical presentation. In very premature infants, attention has focused on deficiencies of surfactant.
1 Evidence indicates that catecholamines secreted by the fetus in response to the stress of normal labor are involved both in the clearance of lung liquid and the secretion of surfactant. 2 The suggestion that surfactant stabilizes a liquid lining on the alveolar surface has been challenged by Hills 3 after measurements of surface tension under physiological conditions. 4 In comparing the chemical structure of pulmonary surfactants with industrial water repellency agents, he has suggested that their role is in keeping the lung dry. The administration of synthetic surfactant may immediately elevate lung compliance in very premature infants.
5 The rapid immediate improvement of oxygenation provides especially in the premature infant provides support for the view that the action of surfactant is in dispelling liquid from the alveolar surface and reversing atlectasis. However, in some infants, oxygenation is delayed and it is likely that this is because of edema. In term, infants there is less consensus on the value of surfactant1 and R.D.S. may occur after a delay when the lungs have been inflated and breathing apparently well established. This delayed form of R.D.S. is associated with pulmonary hypertension, micro-embolism6 and thrombosis, 7 which may be responsible for pulmonary edema, hypoxemia and persistence of the fetal circulation.8
The condition has been compared to the adult respiratory distress syndrome.6 (A.R.D.S.) However, although micro-embolism is now established as the principal cause of the adult syndrome, it has been suggested that the same symptoms in the newborn are due to the presence of amniotic fluid and meconium in the respiratory tract.6 It is notable that the respiratory distress syndrome in the newborn has been modeled experimentally by the intravenous injection of oleic acid.9 It has been stated that only 10 - 20% of brain damaged infants have a history of birth asphyxia and at least half of all brain damaged infants have no scientific explanation for their handicap.10
Although thrombo-emboli found in the lungs of infants with R.D.S. have been attributed to hypoxic damage to cardiac endothelium,6 the emboli may have originated from the placenta. Maternal Amniotic Fluid Embolism: Amniotic fluid embolism is currently a leading cause of maternal death in labor, during delivery and the immediate post-partum period.11 First described by Meyer in 1926,12 maternal pulmonary embolism from placental material was discovered at necropsy by Ceelen in 1931.13 Ten years later, Steiner and Lushbaugh14 reported gross amniotic fluid embolism of the lungs in eight mothers. Death was associated with acute pulmonary edema.
Using the analogy of pulmonary fat embolism, they suggested that minor degrees of embolism, are common and probably not recognized. The lethality has been correlated with the amount and content of particulate matter in the liquor15 and it has been shown experimentally that small amounts of amniotic fluid may be relatively innocuous.16 In a fulminating case, the patient presents with the abrupt onset of severe respiratory distress14 which may be accompanied by evidence of focal cerebral damage or even coma. The damage to the endothelium of the lung, probably due to microemboli and fatty acids in the liquor, causes edema. As a diffusional barrier to oxygen is created, the hypoxia further increases vascular permeability creating a vicious cycle.
Eventually, the organization of extravagated plasma proteins leads to hyaline membrane formation. The pathogenesis is well-established, because of the demonstration of amniotic fluid, meconium and fetal epithelial cells in the maternal blood during life17 and in the lungs at necropsy.14, it is accepted that a defect in the amniotic membranes and the placenta allows the entry of liquor. The particulate matter in amniotic fluid may also escape pulmonary entrapment and embolise other organs, including the kidney, heart and brain,18 and may be the cause of idiopathic cardiomyopathy in pregnancy,17,19 Fetal Placental Embolism: Currently, no clinical syndrome in the newborn is attributed to amniotic fluid or placental embolism.
Steiner and Lushbaugh14 suggested in 1941 that it might be a cause of intra-uterine death, reasoning that, if a defect in the placenta causes embolism in a mother, then it may also be possible in the fetus. They suggested that uterine contraction, after partial placental separation, might force material into the fetal circulation. Their prediction has been proved correct, as fetoplacental thromboembolism has now been described in an intra-uterine death at 32 weeks.20 the vascular organization of the placenta and mechanical factors may confer some protection to the fetus. Although the sinuses of the maternal circulation of the placenta are able to transmit the large quantity of amniotic fluid needed to cause death, the individual vessels in the villi of the fetal circulation are much smaller. It has also been suggested that the high intravillus pressure protects against the transfer of maternal erythrocytes across the placenta,21 although this transfer does sometimes occur.22 Also, when the uterus contracts, the pressures in the whole uterine cavity will increase.
However, only small amounts of material need to enter the fetal circulation to have a serious effect. Villus damage does occur in the placenta and has been correlated with stillbirth23and fetal distress.24 Placental embolism may also be responsible for thrombosis in the umbilical cord. If, as is likely, embolism occurs around the time of delivery, then the permeability of the endothelium of the lung will be increased at this critical time. The presence of atelectasis would be interpreted as evidence that the lungs have not yet inflated and it has been shown experimentally that liquor tends to persist in the newborn lung.25 This, and attempts at resuscitation, may well account for small amounts of amniotic fluid embolism found in the fetal vessels not being attributed to a placental defect.
The pulmonary hypertension and thrombo-embolism, already described in neonates, can be accounted for by the same mechanism as that proven in mothers. In R.D.S., the onset of symptoms may not become significant for some hours, when a high Apgar score has been recorded at delivery. This suggests that pulmonary expansion has taken place normally, but pulmonary edema is developing because of damage to the vascular endothelium. A gradual onset has also been described in maternal amniotic fluid embolism.26 The occurrence of R.D.S. at the time when lung expansion is taking place may have masked the effect of micro-embolism. The risk factors for amniotic fluid embolism and R.D.S. include premature rupture of the membranes, antepartum hemorrhage, and Caesarian section.
If fetal amniotic fluid or placental embolism occurs, together with arterial hypoxaemia, during the transition from the fetal circulation, it represents a worst-case situation. Clinically, R.D.S. may be part of a spectrum, which ranges from the transient tachyponea of the newborn27 to fatal hyaline membrane formation. Amniotic fluid or placental embolism may also be a factor in cerebral pathology in the neonate, especially periventricular leucomalacia and haemorrhage,28 in the watershed territory between the anterior and middle cerebral arteries. Damage to the cerebral white matter is a well-known consequence of micro-embolism.29 In the premature neonate the effect of micro-embolism on an immature blood-brain barrier,30 in the presence of severe hypoxia, may account for the range of white matter pathology described.
Acknowledgements:
References:
- Leading article. Surfactant therapy in the newborn. Lancet 1985;2:867-68.
- Walters DV, Olver RE. The role of catecholamines in lung liquid absorption at birth. Pediatr Res 1978;12:239-42.
- Hills BA. What is the true role of surfactant in the lung? Thorax 1981;36:1-4.
- Barrow RE, Hills BA. Surface tension induced by dipalmitoyl lecithin in vitro under physiological conditions. J Physiol 1979;297:217-27.
- Morley CJ, Bangham AD, Miller N, David JA. Dry artificial lung surfactant and its effect on very premature babies. Lancet 1981;1:64-68.
- Arnold J, O'Brodovich H, Whyte R, Coates G. Pulmonary thromboemboli after neonatal asphyxia. J Pediatr 1985;106:806-9.
- Levin DL, Weinberg AG, Perkin RM. Pulmonary microthrombi syndrome in newborn infants with unresponsive persistent pulmonary hypertension. J Pediatr 1983;102:299-303.
- Riemenschneider TA, Nielsen HC, Ruttenberg HD, Jaffe RB. Disturbances of the transitional circulation :spectrum of pulmonary hypertension and myocardial dysfunction. J Pediatr 1976;89:622-25.
- Pagani G, Rezzonico R, Marini A, Aguggini G. High frequency ventilation in rabbits with experimentally induced R.D.S. In: Cosmi EV, Scarpelli EM eds, Pulmonary surfactant system. Elsevier Science Publishers BV, Amsterdam 1983:151-59.
- Mann LI. Pregnancy events and brain damage. Am J Obstet Gynecol 1986;155:6-9.
- Morgan M. Amniotic fluid embolism. Anaesthesia 1979;34:20-32.
- Meyer JR. Embolia pulmonar amnio-caseosa. Brazil-med 1926;2:301-3.
- Ceelen W, Plazentarzellenembolien. In : Henke F, Lubarsch O, eds. Handbuch der speziellen pathologischen anatomie und histologie. Berlin, Julius Springer 1931;III:98-103.
- Steiner PE, Lushbaugh CC. Maternal pulmonary embolism by amniotic fluid as a cause of obstetric shock and unexpected death in obstetrics. JAMA 1941;117:1245-52, 1340-45.
- Macmillan D. Experimental amniotic fluid infusion. J Obstet Gynaecol Br Comm 1968;75:849-52.
- Adamsons K, Mueller-Heubach E, Myers RE. The innocuousness of amniotic fluid embolism in the pregnant Rhesus monkey. Am J Obstet Gynecol 1971;109:977-80.
- Sherer DM, Menashe M, Elmaleh U. Definitive diagnosis of amniotic fluid embolism with survival. J Obstet Gynaecol 1988;9:45-6.
- Peterson EP, Taylor HB. Amniotic fluid embolism: an analysis of forty cases. Obstet Gynecol 1970; 35:787-93.
- Leading article. Cardiomyopathy and pregnancy. Br Med J 1968;4:269-70.
- Altshuler G, Jordan J. A stillbirth with aspirated squamous pearls and fetoplacental thromboembolism: A new finding and reminder of the importance of placental and fetal pathologic conditions. Am J Obstet Gynecol 1986;155:106-7.
- Malpas P, Symonds EM. Arterial and venous pressures in the human umbilical cord. Am J Obstet Gynecol 1967;98:261-65.
- Cohen F, Zuelzer WW, Evans MM. Transfer of maternal erythrocytes into the fetal circulation. Am J Obstet Gynecol 1965;93:566-69.
- Aladjem S. Phase contrast microscopic observations of the human placenta from six weeks to term. Obstet Gynecol 1968;32:28-39.
- Ornoy A, Crone K, Altshuler G. Pathological features of the placenta in fetal death. Arch Pathol Lab Med 1976;100:367-71.
- Fletcher BD, Sachs BF, Kotas RV. Radiologic demonstration of postnatal liquid in the lungs of newborn lambs. Pediatrics 1970;46:252-4.
- Anderson DG. Amniotic fluid embolism : a re-evaluation. Am J Obstet Gynecol 1967;98:336-48.
- Avery ME, Gatewood OB, Brumley G. Transient tachypnoea of the newborn. Possible delayed resorption of fluid at birth. Am J Dis Child 1966;111: 380-85.
- Leading article. Ischaemia and haemorrhage in the premature brain. Lancet 1984;2:847-8.
- Lumsden CE. Pathogenetic mechanisms in the leucoencephalopathies, anoxic-ischaemic processes and in disorders of the glia and in intoxications. In: Vinken PJ, Bruyn GW eds. Handbook of clinical neurology. Amsterdam North-Holland Publishing Co 1970;572-663.
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