Prognosis of Live Infants Who Have Had Intrauterine Transfusions

RODERIC H. PHIBBS (University of California, San Francisco, Calif.): You can get an erroneous impression of the outcome of a group of intrauterine transfusion survivors if you only examine each child once during infancy or childhood. We have followed a similar though somewhat smaller group, but have examined them every 6 months. This slide shows the mean and the range of developmental and intelligence quotients at different ages in this group. At 6 and 12 months, and to a lesser degree at 18 months, many performed at a retarded level. As they grew older an increasing number achieved normal performance. All those who have reached 3 years of age are now performing at the normal or above-normal level. If such a group had been tested only once, as you did, when many were less than 1.5 years of age, you might have erroneously concluded that many intrauterine transfusion survivors were moderately or severely handicapped. In contrast to your findings, we have not found any evidence of severe physical injury due to the transfusions. The majority of our intrauterine transfusions, however, were done under biplane fluoroscopy where the needle can be guided directly into the abdomen, and this may account for some of the differences in findings. Dr. COCHRAN : In how many of your group did your intrauterine transfusion team not succeed even with their biplane fluoroscopy? Dr. PHIBBS : Dr. ALAN MARGOLIS, who does all the intrauterine transfusions at our institution, tells me that with the use of biplane fluoroscopy he has never failed to get the needle into the abdomen of the fetus, although he does not always succeed on the first attempt. Dr. COCHRAN : I agree that more frequent follow-up might easily have changed our DO and IQ, results. Certainly, as already pointed out, our group went from 6 months to 4.5 years and it is well known that any group tested as early as 6 months of age for IQ puts one on shaky ground. Louis K. DIAMOND (University of California Medical Center, San Francisco, Calif.): I am going to draw on our experience in Boston, not San Francisco, with the same patients reported by Dr. COCHRAN, since our Blood Grouping Laboratory was responsible for the amniotic fluid measurements, all the blood group and blood serum tests on mothers and infants, and the intrauterine transfusion procedure carried out by Dr. EASTERDAY, obstetrician, and Dr. UMANSKY, pediatrician, of the intrauterine transfusion team. These women and their infants, here reported by Dr. Cochran, were, therefore, well known to us up to the time of their delivery. I think Dr. COCHRAN'S paper has merit in pointing out that intrauterine transfusion is neither a simple procedure nor one that is without danger. Therefore, it should only be done when clearly indicated, and the patients should be treated with great care, particularly to avoid infection, which I think has occurred a few times in the 150 or more patients that Dr. EASTERDAY and Dr. UMANSKY have transfused. As to the patients themselves, it is necessary to realize that almost all these infants, based on the past history of the mother, the high levels of antibody, and the amniotic fluid measurements were doomed children; saving only 40 out of 150 would have been quite an accomplishment, especially since some of them were already hydropic at the time of the first intrauterine transfusion. However, beyond that, I fail to see how some of them fit into the category either of death or physical or psychological or intellectual maldevelopment primarily as the result of the intrauterine transfusion. Certainly the myelomeningocele was an unrelated lesion, and possibly the twins, who were both premature and had very low Apgar scores at birth, might have suffered the same sort of damage even if they had never had erythroblastosis or been transfused. It is difficult to understand how the renal damage in two patients could have resulted from the infusion of dye into the kidney substance on one side (the needle unfortunately poked into this and then gave a diffuse nephritis or nephritislike picture which seemed to involve both kidneys); possibly the swallowed dye could do this, though it seems unlikely. After such an analysis, one might conclude that 2 or, at the most, 3 of these patients may have suffered some ill effect from the intrauterine transfusion, but 3 out of 40 is only around 7 or 8 %, whereas your figures suggest almost 20 % trouble in these cases. I would stress, therefore, that intrauterine transfusion, though a difficult and dangerous procedure, is not nearly as hazardous to the physical or mental development of these infants as this report seems to imply. Dr. COCHRAN : I would respond to Dr. DIAMOND by saying that I do agree. These infants are jeopardized from many directions, not just from the intrauterine transfusion. Thus, the data have been presented so that you could make your decision as to where you think the jeopardy would most likely lay. Slowly but surely if we publish all such data we will be able to make some statistical statements in time. For 34-week gestation infants these particular infants have probably done all right; however, it would be better if we could get them up to 37 weeks before delivery, if possible. We have not succeeded on the average, in doing so. Ideally, it would be best to get them up to 40 weeks. On another tack, I have always felt mothers who endure high risk pregnancies tend to have problems of any type in greater percentage than mothers who have normal pregnancies as regards infant outcome. Therefore, we have to include babies even with congenital anomalies so that once again, if we collect a large enough series, in time we can see if there is an increased incidence of one or another problem. Maybe Dr. WARKANY could respond to this possibility. Just to speak again about the kidney lesions, Dr. FELLERS and Dr. CRAIG are in the process of preparing a paper concerning dye injection into rats. In this study, they feel they have shown that if dye is put into the region of one kidney it causes bilateral and comparable kidney lesions. These lesions in the rat are also comparable to those seen in our infants. LEO STERN (The Montreal Children's Hospital, Montreal, Que.): Like Dr. DIAMOND, I am not quite clear why you would impugn the intrauterine transfusion. You have a group of children who are from 28.5 to 37.5 weeks of gestational age. Is there any evidence that the degree of psychological development malfunction that you estimate is any different than that of any ordinary group of 27.5–37.5-week-old infants? The other problem is also something alluded to by Dr. DIAMOND. You are dealing with a group of infants, many of whom have had to be sectioned to get them out ex utero at that age. A number of them probably had to be induced, and much of this is not so much the song as the singer—who does the induction, who does the delivery, and the section. I am not clear as to why the relationship should be to the procedure of intrauterine transfusion. Maybe it is just the prematurity and how they were delivered. Dr. COCHRAN: First of all, Dr. STERN, the one factor that brings these infants together is that they all have had an intrauterine transfusion. I agree that some are more premature than others, and some certainly have many problems to conquer than just the intrauterine transfusion, but all have had intrauterine transfusions. Thus, it is the intrauterine transfusion that puts them in a particular category and selects out those infants we have been discussing here. Except for the three with problems fairly definitely associated with the intrauterine transfusion procedure one cannot say specifically that their problem is due to this procedure or due to the threat to their life for which the procedure is incidentally performed. They still are clinically one group that we would like to make as healthy as possible. Once again, if we collect a pool of such infants who have had this procedure, in time we may have enough data to make some statistical tables that they truly are different—or maybe not different. Obviously most of you think they are not different from the normal run of 28–37-week-old infants. JOHN M.BOWMAN (Winnipeg, Man.): We have transfused 156 fetuses 341 times; 151 have been delivered and we have 80 survivors. Of the 80 survivors, 58 are now more than 1 year old and we have been able to follow 45 of them. Of the 45, we have had 2 severely damaged infants. One was hydropic at delivery, survived 7 exchange transfusions, developed a spontaneous subarachnoid hemorrhage at 19 days of age, had communicating hydrocephalus, has had a shunt, and now has a developmental quotient of 65. The second severely damaged patient was noted to be hydropic at the time of the second fetal transfusion. This hydropic condition was reversed after the third transfusion. This patient was delivered after 34 weeks of gestation, and has been observed to have severe cerebral agenesis. Her parents were not too dissimilar from the parents of the twins that Dr. COCHRAN mentioned because they also were of very low intellect. The remaining 43, as far as we can determine, are well within the normal range. RONALD J. CANTWELL (University of Miami, Miami, Fla.): Dr. COCHRAN may be interested to know that Dr. BILL LILEY'S first case of intrauterine transfusion which I followed up, also had a hemiparesis. Although we did not regard this as a complication of the procedure, I notice that of your 7 survivors who had complications, 1 had hemiparesis. It may be that this is a significant complication of intrauterine transfusion.