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Crossing the chorion: Amniocentesis
EDITOR'S COLUMN
Crossing the cborion: Amniocentesis "The death o[ a human [etus with erythroblastosis [etalis may have been prevented by intrauterine blood trans[used into the [etal peritoneum around the 30th week o[ pregnancy." News item, The Medical Tribune, World Wide Report, Rochester, N. Y.,
March 27, 1964.
T I-I E technique of transfusing the fetus in utero was pioneered by Dr. A. W. Liley of New Zealand in the hope of gaining a few extra weeks of intrauterine gestation by a fetus with progressive Rh sensitization as indicated by a rapidly rising antibody titer in the amniotic fluid. Just as Caesar crossed the Rubicon to defeat Pompey, so the mysteries of amniotic fluid are being revealed to the intrepid scientists who cross the chorion and utilize the information in the conquest of erythroblastosis fetalis. In recent years examination of the amniotic fluid by puncture through the abdominal wall has proved a valuable means of forecasting the severity of erythroblastosis fetalis.l-r, ~0-~2 This method has been useful in management of the sensitized woman who has had one affected infant requiring therapy, when during the current pregnancy there has been a significant rise in antibody titer to at least 1:32. 8 Assessment based on the antibody titer is sometimes misleading, particularly when there has been a moderately or severely affected infant in the past. Mothers previously sensitized to the Rh factor have given birth to Rh-negative
infants despite marked increases in antibody titer during pregnancy. The problem is also accentuated in the case of a husband who is definitely or probably heterozygous. Also, in spite of a rising titer, early delivery may yield an Rh-positive infant without any evidence of erythroblastosis who is subsequently exposed to the risk of prematurity, s Examination of the amniotic fluid might prevent unnecessary deaths and unnecessary caesarean sections with delivery of unaffected children by affording a more realistic evaluation of erythroblastosis in utero than fluctuations in the titer. Transabdominal puncture is carried out in the region of the fetal buttocks or feet and usually in the midline. 5 T o reduce the risk of opening fetal channels, the placenta may be localized by the use of radioactive albumin or chromated red cells. 6 Bloodstained amniotic fluid is discarded but other specimens are tested fresh after eentrifugation and filtration. Aspiration is initially performed at 32 weeks' gestation, and depending on the individual case, may or may not be repeated at 3 week intervaIs. 6 There is frequently an increase in total protein content of the amniotic fluid in cases of isoim642
Volume 65
Number 4
munization, and this concentration tends to increase with the severity of the disease. The increase is in the albumin fraction, but is much less precise than measurement of pigment. Bilirubin appears in the fluid mainly as the indirect type when determined by the van den Burgh reaction. More commonly, the combined pigments which represent various degradation products of hemoglobin, including bilirubin, are measured spectrophotometrically. The optical density is plotted against wave length (/~) and a continuous recording is obtained as the spectrophotometer scans the specimen from 800 to 300 /~.6 The bile pigments degraded from hemoglobin absorb over the range between 400 and 500 ~ and when they are present in significant amounts a bulge appears on the curve, usually at about 450 ~. In general, the more pronounced the bulge, the more severely affected is the fetus. The prognosis is progressively worse the earlier the pigments appear. Severe hemolysis before the thirty-second week invariably presages a fatal outcome. 1 When bilirubin is the sole pigment measured, varying degrees of severity have been set forth as indications for premature induction of labor. For instance, labor is induced with a bilirubin level of 0.3 mg. per 100 ml. and over. 7 Spectrophotometric determinations seem preferable because the total pigments and not bilirubin alone are measured since bilirubin by itself is present in such small concentration. While labor is usually induced at approximately 37 weeks where there is a rapidly rising and excessive titer (i :64), especially with a previously affected erythroblastotic infant, induction has been successfully carried out on the basis of amniocentesis as early as 32 weeks with a viable infant2 Although most workers find amnlocentesis a relatively safe procedure, attention has been drawn to the possibility that fetal erythrocytes might enter the maternal circulation if the placenta were damaged during amniocentesis2 Fetal hemorrhage m a y conceivably result, compromising the life
Editor's column
643
of the fetus and may also precipitate a rise in antibody titer in the mother. On the other hand, in a review of a large number of cases, 1~ no evidence was found that amniocentesis gave rise to changes in maternal antibody titer or increased the severity of hemolytic disease in the current or subsequent pregnancy. It is impossible as yet to state that amniocentesis will never affect the titer or that placental damage may not have some effect in a later pregnancy. In one hospital it was found that after nearly 1,000 taps, complete failure occurred in about 5 per cent of cases and blood staining only in a further 5 per cent. 11 In 9 out of 10 cases this technique was completely without danger to the fetus and was of sufficient value so that the survival rate of infants affected with hemolytic disease had risen approximately one-third. In another hospital, 12 despite an occasional rise in titer following amniocentesis, the value of this procedure was also emphasized. It was felt, however, that in the first immunized pregnancy anti-D titers were generally a good indication of the fetal condition, and amniocentesis was unnecessary. In subsesequent pregnancies or in pregnancies in which immunization was caused by a prior blood transfusion, amniocentesis was of great value because of unreliability of the antibody titer. More extensive experience is, therefore, necessary so that the dangers and benefits of the procedure m a y be evaluated. There are potential dangers in amniocentesis itself, in the premature induction of labor, and in the prematurity of the infant after birth. 7 The objective, of course, is both a drop in the stillbirth rate and a commensurate drop in the neonatal death rate from premature induction. While amniocentesis may never become a routine procedure, it serves in selected cases as an important means of assessing the severity of erythroblastosis fetalis in those cases where fetal life is at risk. CARL H .
SIYnTIt~ M.D.
DEPARTI~,IENT OF PEDIATRICS T H E N E W YORK I-IOSPITAL C O R N E L L U N I V E R S I T Y MEDICAL C E N T E R
644
Editor's column
REFERENCES
I. Bevis, D. C. A.: Blood pigments in haemolytic disease of the newborn, J. Obst. & Gynaec. Brit. Emp. 63: 68, 1956. 2. Walker, A. H. C.: Liquor amnii studies in the prediction of haemolytic disease of the newborn, Brit. M. J. 2: 376, 1957. 3. Cary, W_: Amniocentesis in haemolytie disease of the newborn, M. J. Australia 47: 778, 1960. 4. Liley, A. W.: Liquor amnii analyses in the management of the pregnancy complicated by rhesus sensitization, Am. J. Obst. & Gynec. 82: 1359, 1961. 5. MacKay, E. V.: The management of isoimmunized pregnant women with particular reference to amniocentesis, Australian & New Zealand J. Obst. & Gynaec. 1: 78, 1961. 6. Freda, V. J., and Gorman, J. G.: Current concepts. Antepartum management of Rh hemolytic disease, Bull. SIoane Itosp. for Women 8: 147, 1962.
October 1964
7. MacKay, E. V., and Watson, D.: The diagnostic value of bilirubin levels of amniotie fluid in rhesus isoimmunized pregnancies, M. J. Australia 49: 492, 1962. 8. Gellis, S. S.: Year Book of Pediatrics, 19611962 series, Chicago, 1962, The Year Book Medical Publishers, Inc., p. 298. 9. Zipursky, A., Pollock, J., Chown, B., and Israels, L. G.: Transplacental foetal hemorrhage after placental injury during delivery or amniocentesis, Lancet 2: 493, 1963. 10. Fairweather, D. V. I., Murray, S., Parkin, D., and Walker, W.: Possible immunological implications of amniocentesis, Lancet 2: 1190, 1963. Ii. Jennison, R. F., and Walker, A. H. C.: Amniocentesis, Lancet 2: 1387, 1963. 1387, 1963. I2. Queenan, J. T., and Adams, D. W.: Amniocentesis, Lancet 1: 380, 1964.
Crossing the cborion: Amniocentesis "The death o[ a human [etus with erythroblastosis [etalis may have been prevented by intrauterine blood trans[used into the [etal peritoneum around the 30th week o[ pregnancy." News item, The Medical Tribune, World Wide Report, Rochester, N. Y.,
March 27, 1964.
T I-I E technique of transfusing the fetus in utero was pioneered by Dr. A. W. Liley of New Zealand in the hope of gaining a few extra weeks of intrauterine gestation by a fetus with progressive Rh sensitization as indicated by a rapidly rising antibody titer in the amniotic fluid. Just as Caesar crossed the Rubicon to defeat Pompey, so the mysteries of amniotic fluid are being revealed to the intrepid scientists who cross the chorion and utilize the information in the conquest of erythroblastosis fetalis. In recent years examination of the amniotic fluid by puncture through the abdominal wall has proved a valuable means of forecasting the severity of erythroblastosis fetalis.l-r, ~0-~2 This method has been useful in management of the sensitized woman who has had one affected infant requiring therapy, when during the current pregnancy there has been a significant rise in antibody titer to at least 1:32. 8 Assessment based on the antibody titer is sometimes misleading, particularly when there has been a moderately or severely affected infant in the past. Mothers previously sensitized to the Rh factor have given birth to Rh-negative
infants despite marked increases in antibody titer during pregnancy. The problem is also accentuated in the case of a husband who is definitely or probably heterozygous. Also, in spite of a rising titer, early delivery may yield an Rh-positive infant without any evidence of erythroblastosis who is subsequently exposed to the risk of prematurity, s Examination of the amniotic fluid might prevent unnecessary deaths and unnecessary caesarean sections with delivery of unaffected children by affording a more realistic evaluation of erythroblastosis in utero than fluctuations in the titer. Transabdominal puncture is carried out in the region of the fetal buttocks or feet and usually in the midline. 5 T o reduce the risk of opening fetal channels, the placenta may be localized by the use of radioactive albumin or chromated red cells. 6 Bloodstained amniotic fluid is discarded but other specimens are tested fresh after eentrifugation and filtration. Aspiration is initially performed at 32 weeks' gestation, and depending on the individual case, may or may not be repeated at 3 week intervaIs. 6 There is frequently an increase in total protein content of the amniotic fluid in cases of isoim642
Volume 65
Number 4
munization, and this concentration tends to increase with the severity of the disease. The increase is in the albumin fraction, but is much less precise than measurement of pigment. Bilirubin appears in the fluid mainly as the indirect type when determined by the van den Burgh reaction. More commonly, the combined pigments which represent various degradation products of hemoglobin, including bilirubin, are measured spectrophotometrically. The optical density is plotted against wave length (/~) and a continuous recording is obtained as the spectrophotometer scans the specimen from 800 to 300 /~.6 The bile pigments degraded from hemoglobin absorb over the range between 400 and 500 ~ and when they are present in significant amounts a bulge appears on the curve, usually at about 450 ~. In general, the more pronounced the bulge, the more severely affected is the fetus. The prognosis is progressively worse the earlier the pigments appear. Severe hemolysis before the thirty-second week invariably presages a fatal outcome. 1 When bilirubin is the sole pigment measured, varying degrees of severity have been set forth as indications for premature induction of labor. For instance, labor is induced with a bilirubin level of 0.3 mg. per 100 ml. and over. 7 Spectrophotometric determinations seem preferable because the total pigments and not bilirubin alone are measured since bilirubin by itself is present in such small concentration. While labor is usually induced at approximately 37 weeks where there is a rapidly rising and excessive titer (i :64), especially with a previously affected erythroblastotic infant, induction has been successfully carried out on the basis of amniocentesis as early as 32 weeks with a viable infant2 Although most workers find amnlocentesis a relatively safe procedure, attention has been drawn to the possibility that fetal erythrocytes might enter the maternal circulation if the placenta were damaged during amniocentesis2 Fetal hemorrhage m a y conceivably result, compromising the life
Editor's column
643
of the fetus and may also precipitate a rise in antibody titer in the mother. On the other hand, in a review of a large number of cases, 1~ no evidence was found that amniocentesis gave rise to changes in maternal antibody titer or increased the severity of hemolytic disease in the current or subsequent pregnancy. It is impossible as yet to state that amniocentesis will never affect the titer or that placental damage may not have some effect in a later pregnancy. In one hospital it was found that after nearly 1,000 taps, complete failure occurred in about 5 per cent of cases and blood staining only in a further 5 per cent. 11 In 9 out of 10 cases this technique was completely without danger to the fetus and was of sufficient value so that the survival rate of infants affected with hemolytic disease had risen approximately one-third. In another hospital, 12 despite an occasional rise in titer following amniocentesis, the value of this procedure was also emphasized. It was felt, however, that in the first immunized pregnancy anti-D titers were generally a good indication of the fetal condition, and amniocentesis was unnecessary. In subsesequent pregnancies or in pregnancies in which immunization was caused by a prior blood transfusion, amniocentesis was of great value because of unreliability of the antibody titer. More extensive experience is, therefore, necessary so that the dangers and benefits of the procedure m a y be evaluated. There are potential dangers in amniocentesis itself, in the premature induction of labor, and in the prematurity of the infant after birth. 7 The objective, of course, is both a drop in the stillbirth rate and a commensurate drop in the neonatal death rate from premature induction. While amniocentesis may never become a routine procedure, it serves in selected cases as an important means of assessing the severity of erythroblastosis fetalis in those cases where fetal life is at risk. CARL H .
SIYnTIt~ M.D.
DEPARTI~,IENT OF PEDIATRICS T H E N E W YORK I-IOSPITAL C O R N E L L U N I V E R S I T Y MEDICAL C E N T E R
644
Editor's column
REFERENCES
I. Bevis, D. C. A.: Blood pigments in haemolytic disease of the newborn, J. Obst. & Gynaec. Brit. Emp. 63: 68, 1956. 2. Walker, A. H. C.: Liquor amnii studies in the prediction of haemolytic disease of the newborn, Brit. M. J. 2: 376, 1957. 3. Cary, W_: Amniocentesis in haemolytie disease of the newborn, M. J. Australia 47: 778, 1960. 4. Liley, A. W.: Liquor amnii analyses in the management of the pregnancy complicated by rhesus sensitization, Am. J. Obst. & Gynec. 82: 1359, 1961. 5. MacKay, E. V.: The management of isoimmunized pregnant women with particular reference to amniocentesis, Australian & New Zealand J. Obst. & Gynaec. 1: 78, 1961. 6. Freda, V. J., and Gorman, J. G.: Current concepts. Antepartum management of Rh hemolytic disease, Bull. SIoane Itosp. for Women 8: 147, 1962.
October 1964
7. MacKay, E. V., and Watson, D.: The diagnostic value of bilirubin levels of amniotie fluid in rhesus isoimmunized pregnancies, M. J. Australia 49: 492, 1962. 8. Gellis, S. S.: Year Book of Pediatrics, 19611962 series, Chicago, 1962, The Year Book Medical Publishers, Inc., p. 298. 9. Zipursky, A., Pollock, J., Chown, B., and Israels, L. G.: Transplacental foetal hemorrhage after placental injury during delivery or amniocentesis, Lancet 2: 493, 1963. 10. Fairweather, D. V. I., Murray, S., Parkin, D., and Walker, W.: Possible immunological implications of amniocentesis, Lancet 2: 1190, 1963. Ii. Jennison, R. F., and Walker, A. H. C.: Amniocentesis, Lancet 2: 1387, 1963. 1387, 1963. I2. Queenan, J. T., and Adams, D. W.: Amniocentesis, Lancet 1: 380, 1964.