Irving B. Wexler

Withdrawal symptoms in infants with the fetalalcohol syndrome

Six infants with dysmorphic features of the fetal alcohol syndrome presented with symptoms of withdrawal from alcohol similar to those observed in adults and animals. Symptoms were characterized by irritability, tremors, spontaneous seizures, opisthotonos, and abdominal distention. A comparison of symptoms is made to animal and withdrawal from ethanol and to the neonatal narcotic withdrawal syndrome.

The Fetal Alcohol Syndrome: Some Maternal Characteristics

The characteristics of eight mothers of ten infants born with typical features of the fetal alcohol syndrome (FAS) are presented. These chronic alcoholic mothers have poor obstetric histories, tend to have poor or no prenatal care and may repeat pregnancies which result in infants with FAS. Family planning counseling appears unhelpful.

Treatment of erythroblastosis fetalis by exchange transfusion: Statistical analysis of results*

Summary Among thirty-six stillbirths causedby Rh sensitization, all but one of the patients had Rh antibody titers of 16 units or higher by the albumin-plasma conglutination method. (In the single exceptional case, where the albuminplasma titrations were negative, it was possible to show that antibodies were present, but of an unusual type, since the titer was high by the antiglobulin and enzyme techniques.) Therefore, when using antibody titer as a criterion of severity, it was decided to consider 8 units by the albumin-plasma titration method as the upper limit for cases classified as “mildly” affected. The results of treatment by exchange transfusion in a series of 222 erythroblastotic infants were compared with the results obtained in a series of sixty-seven erythroblastotic babies who were left untreated or given one or more simple transfusions. Among “mildly” affected babies, i.e., those whose mothers had antibody titers of 8 units or less, no significant difference in the mortality rate in the two series was demonstrable. On the other hand, among severely affected babies treated by exchange transfusion, the mortality rate was 15.5±2.0 per cent, while among the babies receiving simple transfusions or no treatment, the mortality rate was as high as 46.4±6.2 per cent. The difference in mortality rate, 28.9±6.5 per cent, is statistically significant. During the past few years changeshave been introduced into our method of carrying out exchange transfusions. In the method now used by us, part of the citrated plasma is removed from bank blood not more than three days old, which has been allowed to sediment in the refrigerator in order to reduce the volume to 400 ml., and the resulting concentrated blood (hematocrit, approximately 0.50) is used for the exchange transfusion, equal volumes of blood being withdrawn and injected. In more severely affected babies, a second such exchange transfusion is given twenty-four to forty-eight hours after birth. Among seventy-eight erythroblastotic babics treated in this way, of whom fifty-three had mothers with antibody titers above 8 units by the albumin-plasma method, the mortality rate was only 5.1±1.6 per cent. (In this discussion, mortality rate is used to include neurological sequelae as well as deaths.) Case reports are presented in orderto illustrate the course of Rh sensitization in women followed through several pregnancies and to compare the results of treatment of several erythroblastotic babies born to the same mother. A case is cited which demonstrates the importance of icterus per se as a criterion of severity, and therefore this sign is a strong indication for treatment by exchange transfusion even in the absence of anemia. In view of the innocuousness of exchange transfusion carried out by the radial artery-saphenous vein technique and the excellent results obtained by this treatment, our tendency has been to widen the indications for its use in treating erythroblastotic babies.

Treatment of erythroblastosis fetalis, with special reference to sensitization to Rh-Hr factors other than Rh0

Summary To date, 166 babies with erythroblastosis fetalis caused by Rh 0 sensitization have been treated by our latest modification of exchange transfusion by the radial artery-saphenous vein technique. In this latest modification, partially concentrated blood (hematocrit 0.5), preferably not more than three days old, is used. This is prepared by removing part of the citrated plasma after sedimentation has occurred. Depending on the severity of the disease and the size of the baby, from 450 to 900 ml. of such concentrated blood is used for the transfusion. In severe cases the exchange transfusion is repeated. In no instance are more than two exchange transfusions deemed necessary. Among the 166 babies treated this way, only five babies died or had neurological sequelae, a crude mortality rate of only 3.0±0.9 per cent. On the other hand, among babies treated by our earlier modifications, or by only simple transfusion, or receiving no treatment at all, the mortality rate ranged from 17 to 21 per cent. The difference in results is even more striking when the severity of the disease is taken into account. Thus, among severely affected babies who received no treatment the mortality rate was 65.5±10.6 per cent; among those receiving simple transfusion therapy the mortality rate was 42.1±7.8 per cent; among those treated by our previous methods of exchange transfusion the mortality rate was 19.8±2.6; while among those treated by our latest modification of exchange transfusion, the mortality rate was only 3.8±1.0 per cent. The cases of erythroblastosis fetalis caused by sensitization to Rh-Hr factors other than Rh 0 pose an important problem, since the routine antenatal screening test for Rh 0 sensitization does not take them into account. Such cases are rare, but when they occur they are just as serious as instances of Rh 0 sensitization. Thus, among nine cases of erythroblastosis fetalis caused by hr′ sensitization, one baby died before treatment could be instituted. Of the remainder, four were treated by exchange transfusion and recovered uneventfully, while among the four treated by simple transfusion one died and one of the three who survived had severe neurological sequelae. A simple screening test for Rh 0 antibodies consists in testing the serum of the patient against ficin-treated cells of types Rh 1 Rh 1 , Rh 2 , and rh, respectively. This test should be carried out on all patients in labor admitted to the obstetrical service, and on patients admitted to the surgical or other services, who might require blood transfusion therapy. Case histories are presented, which illustrate the value of this screening test. It is pointed out that in cases of hr′ sensitization the antibodies, even when present in high titer, may react only in tests against enzyme-treated cells and may fail to react in the conglutination and antiglobulin tests. This accounts for puzzling, severe cases of erythroblastosis fetalis in which the direct antiglobulin test for coating of the babys red cells by Rh-Hr antibodies is negative. It is emphasized that certain antibodies, such as anti- F and anti- J are not detected by the enzyme test, so that the screening test against ficin-treated cells should supplement and not replace the other tests for isosensitization.

Blood-group factors and physiological icterus.

There is a close similarity in the hypotensive effects of pentaand hexa-methonium bromides, though formal tests show that hexamethonium bromide is usually slightly stronger in action. We have experienced no difficulty in interchanging these substances at approximately the same level of subcutaneous dosage. Falls in blood pressure following pentaor hexamethonium injections are influenced by posture, being greater as the patient approaches the vertical. Under comparable conditions patients with the higher pressures tend to have the greater blood-pressure falls after hexamethonium bromide injections. Following sufficiently large injections of these methonium halides, the casual blood pressure falls below the original level of the basal blood pressure, and may be well below this level even in the horizontal posture. The effects of pentaand hexa-methonium injections on the pulse rate are not constant, but usually as the blood pressure falls the pulse rate increases. This statement applies to the blood-pressure changes induced by changes in posture. Sensitivity tests to hexamethonium bromide have been carried out in 150 cases of high blood pressure, including 72 cases of fixed and 15 labile types of essential hypertension; 11 following sympathectomy ; 11 patients with malignant hypertension; 21 with hypertension following pregnancy toxaemia; two with acute pregnancy toxaemia; 10 with impairment of renal function following surgical disorders of the kidney or nephritis ; one case of hypertension associated with polycythaemia; and seven cases of miscellaneous aetiology. Poor response to pentaor hexamethonium salts has so far been restricted to certain cases of renal damage; other cases with renal damage showed good blood-pressure falls. Fifty-three of the more severe cases were treated, and we have been able to maintain a substantial measure of control over the blood-pressure level. On the basis of 150 test doses and treatment of 53 cases we would judge that, apart from some of the cases with impairment of renal function, almost all hypertensives can have their blood pressure controlled by these drugs. Among those with impaired renal function the four selected for treatment were readily brought under control without deterioration in their renal excretory capacity as judged by the T.N.P.N. estimations. Repeated administration gives rise to considerable tolerance, such that 5 or 10 times the original dose may be required to produce the same effect. The acquisition of tolerance to hexamethonium bromide conveys an equivalent degree of tolerance to pentamethonium bromide, and vice versa. Following repeated administration of pentaor hexamethonium salts, patients who at the outset exhibit symptoms such as faintness on blood-pressure reduction usually become more tolerant of the lower blood-pressure levels. The hypotensive actions of pentaand hexa-methonium salts are enhanced on a salt-poor diet (0.2 g. of sodium in 24 hours) to such a degree that dangerous reactions may occur if the effects of this potentiation are not allowed for in determining dosage. Hypertensive headaches can be relieved in most patients. The relief of signs and symptoms, when present, in cases treated over a period of months was prompt and striking. Particular reference has been made to the marked improvement of dyspnoea under treatment, and to the disappearance of papilloedema and retinal exudates. Pulmonary congestion disappeared, and there are indications of reduction in heart size and electrocardiographic improvement. We desire to express our gratitude to Sister R. Wilson and Sister J. Woods; to Miss J. Rivers, Mrs. M. McLachlan, Miss A. Tunbridge, and Mr. C. Drake for technical help; to Miss M. Walsh and Miss M. Poppelwell for secretarial assistance; to Dr. W. R. Thrower, of May and Baker Ltd., who, knowing of our interest in other quaternary ammonium compounds, arranged for us to be supplied with pentaand hexa-methonium salts. Thanks are due to Dr. J. A. Kilpatrick for permission to quote in Table III work undertaken in collaboration with one of us. The expenses were defrayed in part by the Medical Research Council of New Zea!and.

A Pair of Male Fraternal Twins with Contrasting Manifestations of Rh Hemolytic Disease

A pair of male, Negro, fraternal twins are described, both of whom were affected with Rh hemolytic disease. In one twin, the manifestations were typical; jaundice appeared early, exchange transfusion was carried out, and this was followed by prompt and complete recovery. In the second twin, who was treated expectantly, jaundice appeared later and followed the protracted course of the so-called «inspissated bile» syndrome, i. e., the stools were acholic, there was bile in the urine, and most of the serum bilirubin was of the direct reacting type. Of interest was the finding that the occurrence of the syndrome was presaged by the presence of excessive amounts of direct reacting bilirubin in the cord serum. This twin also recovered completely, but convalescence was more prolonged. The observations on these twins provide further evidence that the constitution of the baby, in addition to the maternal Rh antibody titer determine the nature and severity of the manifestations in an erythroblastotic baby.