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Intrauterine exchange transfusion
Intrauterine exchange transfusion STANLEY H. ASEKSIO, M.D. JUAN G. FIGUEROA-LONGO, M.D . IVAN A. PELEGRINA, M.D. San Juan, Puerto R ico
THE MAN AGE MEN T of the rhesussensitized women who give birth to severely affected or stillborn infants has been a great disappointment until recently. It has depended primarily on the past obstetrical history and the level of the maternal antibody titers. The spectrophotometric scanning of the amniotic fluid introduced by Bevis3 in 1952, with the additional information obtained from the work of Liley,12 Freda,s, 9 and others,4, 6, 15 has permitted a more accurate assessment of the state of the fetus in utero and of the prognosis for its survival. In 1963, Liley12 reported an ingenious method by which he was able to carry out intrauterine fetal transfusion. This method has been carried out and further modified to include repeated transfusions and indwelling intraperitoneal catheterization. Later in 1963, Freda and Adamsons1 performed, successfully, the first intrauterine exchange transfusion. Unfortunately, labor ensued 36 hours after the procedure and the pregnancy terminated with a vaginal delivery of a 27 week fetus which died of immaturity and incomplete expansion of the lungs. Evaluation of the available information led us to believe that Freda and Adamsons' approach was the most physiologically suited for the correction of the anemia in severely affected fetuses, and preparations were made to employ it in our hospital, in the treatment of a patient. The following is the report of the case.
Mrs. A. R. P., a 26-year-old white Puerto Rican, gravida viii, para vi, with one abortion and no living children, was admitted to the Hospital of the University of Puerto Rico School of Medicine, on July 14, 1965. She was then in the twenty-fifth week of pregnancy. The patient was Rh negative and her husband was homozygous Rh positive. She had been sensitized by a blood transfusion given at the age of 9 years. Her 6 viable pregnancies had terminated unsuccessfully due to erythroblastosis fetalis (Table I ) . An initial spectrophotometric scanning of the amniotic fluid showed an affected fetus classified, according to Freda,9 as 2+ and placed, according to Liley,lO, 11, 14 in zone C. Repeated weekly examinations confirmed the initial findings and suggested that there was progression of the disease, with increasing jeopardy of the fetus (Figs. 1 and 2) . A decision was made to carry out the planned procedure of . intrauterine exchange transfusion. The patient was started on isoxsuprine hydrochloride (Vasodilan) 10 mg. per os, every 6 hours for 48 hours, in an attempt to decrease uterine contractility.5 The placenta was localized in the left anterolateral wall by amniography with 20 C.c. of radiopaque medium (Hypaque-
Table I. Obstetrical history
I I l Y ear
H'eeks' gestation
1956
40
2
1957
12
3 4 5 6 7
1958 1959 1960 1961 1963 1965
34 30 30 29 28 34
No.
From the Department of Obstetrics and Gynecology of the University of Puerto Rico School of Medicine.
8
1129
Delivery
Born alive, died 3 days old Abortion, dilatation and curettage Stillbirth Stillbirth Stillbirth Stillbirth Stillbirth Present delivery
1130
August J:" 1%6 Am. J. Obs!. & Gynec.
Asensio, Figueroa-longo, and Pelegrina
1.0 0.9 - - 29 WEEKS
0.8
----- 30 WEEKS ---·31 WEEKS
0.7
>ftJ)
_x_
:31.5WEEKS
0 .6 .
Z
w
0
0.5
.....J
U f-
0.4
0
0 .3
ll.
0 .2 0.1
350
400
450
500
550
IoIILLIIIICROillS
WAVELENGTH Fig. 1. Spectral absorption curves of amniotic fluid of a sevcrely affected fetus at diffcrellt gestational ages. All four curves are represented together coinciding with 350 and 550 mJL readings so as to make morc obvious the 450 mJl peak difference. M) and these findings confirmed with scanning technique using radioiodinated serum albumin. Under fluothane anesthesia, a routine approach for cesarean operation was carried out. Intraabdominal external exploration of the uterus revealed a vertex presentation. A gentle external podalic version was done in order to bring the legs into better position for the planned procedure. A vertical uterine incision 4 cm. long was made on the right anterior wall of the corpus, 6 cm. below and 4 cm. medial to the right cornu. The membranes were exposed and gently separated from the underlying decidua to a distance of 3 cm. Angle sutures were taken at the ends of the incision. A continuous lock suture was applied to each border of the uterine incision, tied, and held at the beginning and at the termination of each suture. Thus, when these sutures were tensed and the uterine incision borders lifted, a well-like pocket was formed which was of paramount importance in preventing amniotic fluid loss (Fig. 3). The amniotic sac was incised and the left leg delivered up to the inguinal area. As the leg
and thigh emerged, the pouch was relaxed, and the incision tamponaded with the thigh. A lead for fetal electrocardiogram was applied to the fetal heel for continuous monitoring of fetal heart rate and electrocardiographic tracing. A cut-down was done with exposure of the great saphenous vein just below its junction with the femoral vein. A No. 22 polyethylene catheter was inserted into the great saphenous vein and secured into it (Fig. 4). An exchange transfusion of 160 C.c. of fresh O-negative citra ted packed red cells, compatible with maternal serum was carried out. The blood was withdrawn and injected in increments of 5 c.c. The exchange lasted 3 hours. Every 15 minutes samples were tested for hematocrit, bilirubin, and direct Coombs (Fig. 5). The end point planned for the transfusion was a hematocrit of 50 per cent or better, and a negative direct Coombs determination in the fetal blood. The reversion of the Coombs was obtained but the hematocrit was only raised to 46 per cent after 75 C.c. of transfusion and then remained in a plateau. The blood type, which was initially
Volume 95 Number 8
Intrauterine exchange transfusion
o pOSItIve, became 0 negative. At this time, it was estimated that between 75 and 80 per cent of the fetal blood had been exchanged and the procedure was stopped. The polyethylene cathetcr was removed, the vein tied, and the cutdown closed with interrupted subcutaneous chromic No. 3-0 suture. The "pouch" was again pulled up and the leg reinserted into the amniotic cavity. The amniotic sac was closed in a " purse string" fashion using chromic Xo. 3-0 atraumatic smure. Angle sutures were held up 1.00
0.50
. "
,', ,
.,.'
.
~
..: w 0.20
n.
~
...
'S"
0.10
0
~
f-
iii
z
w
0.05
0
-'
~
l-
n. 0
OO'j A 0.01
28
31
34
37
WEEKS OF GESTATION
Fig. 2. Behavior of the 450 mIL peaks shown in Fig. 1. The four samples are in zone C which corresponds to a severely affected fetus. (Freda's classification +2, +3.)
1131
while the locked sutures at the lateral borders of the incision were removed. The incision was closed in two layers of interrupted sutures followed by a subserosal continuous suture of similar material. The abdominal cavity was closed in layers as in cesarean sections. Postoperatively the patient received 5 mg. isoxsuprine hydrochloride intramuscularly every 3 hours (total dose 40 mg. per 24 hours), and was placed on prophylactic antibiotics. Fetal heart tones, uterine irritability and vital signs were evaluated and recorded every hour for the first 72 hours and then every 4 hours. On the twentieth postoperative day vaginal passage of clear amniotic fluid began spontaneously. The pregnancy was terminated 36 hours after rupture of the membranes, three weeks after the initial procedure, and while the patient was in the thirty-fourth week of gestation. A low cervical vertical cesarean section was done under spinal anesthesia. A living female infant was delivered in good condition, with an Apgar of 8 at 1 minute and of 9 at 5 minutes . The birth weight was 4 pounds, 7% ounces (2,034 grams). The newborn infant had no evidence of edema, although the liver edge was felt 3 cm. below the right costal margin and the spleen was felt 4 cm. below the left costal margin. The area of the cut-down had healed normally. The area of previous uterine incision was barely noticeable externally and without defects in the muscle. The placenta weighed 14 ounces and measured 26 x 18 x 1Y2 cm. Its maternal surface was pale pink with occasional hemorrhagic areas and patchy hyaline deposition. There were no ruptures in the amniotic sac other than the old site of previous surgery which still contained one stitch. This area measured 5
Fig. 3. Diagrammatic representation of uterine muscle pouch used to deliver and reposition the fetal extremity with minimal spillage of amniotic fluid. The angle sutures (shown untied in the figure) were tied in the procedure. Notice continuous locked sutures on both borders of the incision used for hemostasis and traction.
1132 Asensio, Figueroa-Longo, and Pelegrina
Am.
J.
August 15, 1966 Obst. & Gynec.
Fig. 4:. Left fetal leg protruding through the uterine pouch while doing intrauterine exchange transfusions. Electrode to fetal heel is shown. Kotic.e suture ends under traction to avoirl amniotic fluid spillage.
..J ~
z
50
.---------.__ .. ---- .... -... HE~ATOCRIT
10
I fT1
:i!:
40
>-
-i
0
n
;U
30 /
,
20
+
.. .___.__==::J
NEGATIVE
POSITIVE
I
I -I
WEAKLY POSITIVE
25
50
75
100
-i
~
Rh DIRECT
• . COOMBS
125
150
ML.
ACCUMULATIVE VOLUME OF BLOOD EXCHANGED Fig. 5. Hematocrit and total bilirubin values of a 31.5-week-old erythroblastotic fetus during an intrauterine exchange transfusion . (Bilirubin fluctuations up to ±2 mg. are within error of the laboratory.) Changes in Rh and indirect Coombs values are illustrated. cm. in diameter. There was no evidence of edema. Microscopically there were no areas of fibrosis, or evidence of healing in the sutured amniotic sac. The uterus and abdomen were closed in layers. The patient had an uncomplicated postoperative course. The fetus underwent an immediate exchange transfusion in the operating room. The blood samples taken at the beginning of the exchange transfusion showed the fetus to be still 0 negative, the direct Coombs slightly posltlVe, the total bilirubin 12 mg. per cent, and the hematocrit 32 per cent.
Two additional exchange transfusions were given during the next 48 hours. At no time was there any evidence of respiratory distress or s<'psis. Both mother and fetus were discharged on the eighteenth postoperative day. The baby's discharge weight was 5 pounds.
Observations and comments This patient shows a typical case of an Rh-negative sensitized female with a poor obstetrical history and a worse obstetrical prognosis. We were confronted with either
Volume 95 :'IIumbcr 8
terminating the pregnancy for a baby that weighed approximately 2 pounds or using one of the methods described in the literature for intrauterine transfusions or intrauterine exchange transfusions. In our opinion, the intrauterine exchange transfusion as described by Freda and Adamsons 7 was the most physiologic and one in which the condition of the fetus could be accurately assessed. To their technique as described/· 7 few modifications were added. 1. The use of isoxsuprine hydrochloride prior, during, and after surgery for prevention of uterine contractions. 2. The prevention of amniotic fluid spillage while delivering and reinserting the fetal extremity by gentle traction on the suture ends of the uterine pouch. 3. The use of the greater saphenous vein instead of the artery. 4. The use of citrated blood instead of heparinized blood. 5. The closure of the amniotic sac in a purse string fashion. We used the vein instead of the artery in order to avoid arterial circulatory disturbances. Citrated blood, although lowering the pH, was preferred over heparinized blood, so as to decrease unwarranted fetal bleeding.
REFERENCES
1. Adamsons, K., Jr., Freda, V. F., James, L. S. and Towell, M. E.: Pediatrics 35: 848, 1965. 2. Allen, F. H ., and Diamond, L. K. : New England J. Med . 257: 761, 1957. 3. Bevis, D . C. A.: Lancet 1: 395, 1952. 4. Crosby, W. M., and Merrill, J. A.: AM. J. OBST. & GVNEC. 92: 53, 1965. 5. Eriksson, G., and Wiqvist, N.: AM. J. OBST. & GVNEC. 91: 1076, 1965. 6. Fairweather, D. V. I., and Walker, W.: J. Obst. & Gynaec. Brit. Comm. 71: 48, 1964. 7. Freda, V. J., and Adamsons, K., Jr.: AM. J. OBST. & GVNEC. 89: 817, 1964. 8. Freda, V. J., and Gorman, J. G.: Bull. Sloane Hosp. Women 8: 147, 1962.
Intrauterine exchange transfusion
1133
The ammotlc sac was closed in a purse string fashion. On microscopic examination of the suture line there was no histologic evidence of fibrosis or scar formation, even in the area of the amniotic sac still containing a suture. Cultures taken from amniotic fluid, uterine cavity, umbilical cord, fetal skin, fetal gastric contents, and blood exchanged were negative. Blood samples for pH, pC0 2 , and p02 were periodically obtained during the intrauterine exchange procedure but technical difficulties with the instruments prevented the analysis of such data. The absence of premature labor, the minimal trauma sustained by the fetus, and the relatively long-term correction of the anemia have Jed us to believe that this procedure might be the safest and the one that can provide most definite treatment for the severely affected erythroblastotic fetuses. Further knowledge of human fetal physiology is, however, necessary, to widen the scope of this rather promising field of research and treatment. Weare deeply in debt to Drs. H. Rodriguez de Curet, N. de Jesus, A. Martinez Pico, and L. Diaz Bonet, S. Kaye, and to Mr. J. Perez for their assistance and help.
9. Freda, V. J.: AM. J. OBST. & GVNEC. 92: 341, 1965. 10. Liley, A. W.: AM. J. OBST. & GVNEC. 82: 1359, 1961. 11. Liley, A. W.: AM. J. OBST. & GVNEC. 86: 845, 1963. 12. Liley, A. W.: Brit. M . J. 2: 1107, 1963. 13. Liley, A. W.: Pediatrics 35: 836, 1965. 14. Liley, A. W.: Amniocentesis and amniography in hemolytic disease. Year Book of Obstetrics and Gynecology, Chicago, 1964, Year Book Medical Publishers. 15. Walker, A. H. C.: Brit. M. J. 2: 376, 1957.
THE MAN AGE MEN T of the rhesussensitized women who give birth to severely affected or stillborn infants has been a great disappointment until recently. It has depended primarily on the past obstetrical history and the level of the maternal antibody titers. The spectrophotometric scanning of the amniotic fluid introduced by Bevis3 in 1952, with the additional information obtained from the work of Liley,12 Freda,s, 9 and others,4, 6, 15 has permitted a more accurate assessment of the state of the fetus in utero and of the prognosis for its survival. In 1963, Liley12 reported an ingenious method by which he was able to carry out intrauterine fetal transfusion. This method has been carried out and further modified to include repeated transfusions and indwelling intraperitoneal catheterization. Later in 1963, Freda and Adamsons1 performed, successfully, the first intrauterine exchange transfusion. Unfortunately, labor ensued 36 hours after the procedure and the pregnancy terminated with a vaginal delivery of a 27 week fetus which died of immaturity and incomplete expansion of the lungs. Evaluation of the available information led us to believe that Freda and Adamsons' approach was the most physiologically suited for the correction of the anemia in severely affected fetuses, and preparations were made to employ it in our hospital, in the treatment of a patient. The following is the report of the case.
Mrs. A. R. P., a 26-year-old white Puerto Rican, gravida viii, para vi, with one abortion and no living children, was admitted to the Hospital of the University of Puerto Rico School of Medicine, on July 14, 1965. She was then in the twenty-fifth week of pregnancy. The patient was Rh negative and her husband was homozygous Rh positive. She had been sensitized by a blood transfusion given at the age of 9 years. Her 6 viable pregnancies had terminated unsuccessfully due to erythroblastosis fetalis (Table I ) . An initial spectrophotometric scanning of the amniotic fluid showed an affected fetus classified, according to Freda,9 as 2+ and placed, according to Liley,lO, 11, 14 in zone C. Repeated weekly examinations confirmed the initial findings and suggested that there was progression of the disease, with increasing jeopardy of the fetus (Figs. 1 and 2) . A decision was made to carry out the planned procedure of . intrauterine exchange transfusion. The patient was started on isoxsuprine hydrochloride (Vasodilan) 10 mg. per os, every 6 hours for 48 hours, in an attempt to decrease uterine contractility.5 The placenta was localized in the left anterolateral wall by amniography with 20 C.c. of radiopaque medium (Hypaque-
Table I. Obstetrical history
I I l Y ear
H'eeks' gestation
1956
40
2
1957
12
3 4 5 6 7
1958 1959 1960 1961 1963 1965
34 30 30 29 28 34
No.
From the Department of Obstetrics and Gynecology of the University of Puerto Rico School of Medicine.
8
1129
Delivery
Born alive, died 3 days old Abortion, dilatation and curettage Stillbirth Stillbirth Stillbirth Stillbirth Stillbirth Present delivery
1130
August J:" 1%6 Am. J. Obs!. & Gynec.
Asensio, Figueroa-longo, and Pelegrina
1.0 0.9 - - 29 WEEKS
0.8
----- 30 WEEKS ---·31 WEEKS
0.7
>ftJ)
_x_
:31.5WEEKS
0 .6 .
Z
w
0
0.5
.....J
U f-
0.4
0
0 .3
ll.
0 .2 0.1
350
400
450
500
550
IoIILLIIIICROillS
WAVELENGTH Fig. 1. Spectral absorption curves of amniotic fluid of a sevcrely affected fetus at diffcrellt gestational ages. All four curves are represented together coinciding with 350 and 550 mJL readings so as to make morc obvious the 450 mJl peak difference. M) and these findings confirmed with scanning technique using radioiodinated serum albumin. Under fluothane anesthesia, a routine approach for cesarean operation was carried out. Intraabdominal external exploration of the uterus revealed a vertex presentation. A gentle external podalic version was done in order to bring the legs into better position for the planned procedure. A vertical uterine incision 4 cm. long was made on the right anterior wall of the corpus, 6 cm. below and 4 cm. medial to the right cornu. The membranes were exposed and gently separated from the underlying decidua to a distance of 3 cm. Angle sutures were taken at the ends of the incision. A continuous lock suture was applied to each border of the uterine incision, tied, and held at the beginning and at the termination of each suture. Thus, when these sutures were tensed and the uterine incision borders lifted, a well-like pocket was formed which was of paramount importance in preventing amniotic fluid loss (Fig. 3). The amniotic sac was incised and the left leg delivered up to the inguinal area. As the leg
and thigh emerged, the pouch was relaxed, and the incision tamponaded with the thigh. A lead for fetal electrocardiogram was applied to the fetal heel for continuous monitoring of fetal heart rate and electrocardiographic tracing. A cut-down was done with exposure of the great saphenous vein just below its junction with the femoral vein. A No. 22 polyethylene catheter was inserted into the great saphenous vein and secured into it (Fig. 4). An exchange transfusion of 160 C.c. of fresh O-negative citra ted packed red cells, compatible with maternal serum was carried out. The blood was withdrawn and injected in increments of 5 c.c. The exchange lasted 3 hours. Every 15 minutes samples were tested for hematocrit, bilirubin, and direct Coombs (Fig. 5). The end point planned for the transfusion was a hematocrit of 50 per cent or better, and a negative direct Coombs determination in the fetal blood. The reversion of the Coombs was obtained but the hematocrit was only raised to 46 per cent after 75 C.c. of transfusion and then remained in a plateau. The blood type, which was initially
Volume 95 Number 8
Intrauterine exchange transfusion
o pOSItIve, became 0 negative. At this time, it was estimated that between 75 and 80 per cent of the fetal blood had been exchanged and the procedure was stopped. The polyethylene cathetcr was removed, the vein tied, and the cutdown closed with interrupted subcutaneous chromic No. 3-0 suture. The "pouch" was again pulled up and the leg reinserted into the amniotic cavity. The amniotic sac was closed in a " purse string" fashion using chromic Xo. 3-0 atraumatic smure. Angle sutures were held up 1.00
0.50
. "
,', ,
.,.'
.
~
..: w 0.20
n.
~
...
'S"
0.10
0
~
f-
iii
z
w
0.05
0
-'
~
l-
n. 0
OO'j A 0.01
28
31
34
37
WEEKS OF GESTATION
Fig. 2. Behavior of the 450 mIL peaks shown in Fig. 1. The four samples are in zone C which corresponds to a severely affected fetus. (Freda's classification +2, +3.)
1131
while the locked sutures at the lateral borders of the incision were removed. The incision was closed in two layers of interrupted sutures followed by a subserosal continuous suture of similar material. The abdominal cavity was closed in layers as in cesarean sections. Postoperatively the patient received 5 mg. isoxsuprine hydrochloride intramuscularly every 3 hours (total dose 40 mg. per 24 hours), and was placed on prophylactic antibiotics. Fetal heart tones, uterine irritability and vital signs were evaluated and recorded every hour for the first 72 hours and then every 4 hours. On the twentieth postoperative day vaginal passage of clear amniotic fluid began spontaneously. The pregnancy was terminated 36 hours after rupture of the membranes, three weeks after the initial procedure, and while the patient was in the thirty-fourth week of gestation. A low cervical vertical cesarean section was done under spinal anesthesia. A living female infant was delivered in good condition, with an Apgar of 8 at 1 minute and of 9 at 5 minutes . The birth weight was 4 pounds, 7% ounces (2,034 grams). The newborn infant had no evidence of edema, although the liver edge was felt 3 cm. below the right costal margin and the spleen was felt 4 cm. below the left costal margin. The area of the cut-down had healed normally. The area of previous uterine incision was barely noticeable externally and without defects in the muscle. The placenta weighed 14 ounces and measured 26 x 18 x 1Y2 cm. Its maternal surface was pale pink with occasional hemorrhagic areas and patchy hyaline deposition. There were no ruptures in the amniotic sac other than the old site of previous surgery which still contained one stitch. This area measured 5
Fig. 3. Diagrammatic representation of uterine muscle pouch used to deliver and reposition the fetal extremity with minimal spillage of amniotic fluid. The angle sutures (shown untied in the figure) were tied in the procedure. Notice continuous locked sutures on both borders of the incision used for hemostasis and traction.
1132 Asensio, Figueroa-Longo, and Pelegrina
Am.
J.
August 15, 1966 Obst. & Gynec.
Fig. 4:. Left fetal leg protruding through the uterine pouch while doing intrauterine exchange transfusions. Electrode to fetal heel is shown. Kotic.e suture ends under traction to avoirl amniotic fluid spillage.
..J ~
z
50
.---------.__ .. ---- .... -... HE~ATOCRIT
10
I fT1
:i!:
40
>-
-i
0
n
;U
30 /
,
20
+
.. .___.__==::J
NEGATIVE
POSITIVE
I
I -I
WEAKLY POSITIVE
25
50
75
100
-i
~
Rh DIRECT
• . COOMBS
125
150
ML.
ACCUMULATIVE VOLUME OF BLOOD EXCHANGED Fig. 5. Hematocrit and total bilirubin values of a 31.5-week-old erythroblastotic fetus during an intrauterine exchange transfusion . (Bilirubin fluctuations up to ±2 mg. are within error of the laboratory.) Changes in Rh and indirect Coombs values are illustrated. cm. in diameter. There was no evidence of edema. Microscopically there were no areas of fibrosis, or evidence of healing in the sutured amniotic sac. The uterus and abdomen were closed in layers. The patient had an uncomplicated postoperative course. The fetus underwent an immediate exchange transfusion in the operating room. The blood samples taken at the beginning of the exchange transfusion showed the fetus to be still 0 negative, the direct Coombs slightly posltlVe, the total bilirubin 12 mg. per cent, and the hematocrit 32 per cent.
Two additional exchange transfusions were given during the next 48 hours. At no time was there any evidence of respiratory distress or s<'psis. Both mother and fetus were discharged on the eighteenth postoperative day. The baby's discharge weight was 5 pounds.
Observations and comments This patient shows a typical case of an Rh-negative sensitized female with a poor obstetrical history and a worse obstetrical prognosis. We were confronted with either
Volume 95 :'IIumbcr 8
terminating the pregnancy for a baby that weighed approximately 2 pounds or using one of the methods described in the literature for intrauterine transfusions or intrauterine exchange transfusions. In our opinion, the intrauterine exchange transfusion as described by Freda and Adamsons 7 was the most physiologic and one in which the condition of the fetus could be accurately assessed. To their technique as described/· 7 few modifications were added. 1. The use of isoxsuprine hydrochloride prior, during, and after surgery for prevention of uterine contractions. 2. The prevention of amniotic fluid spillage while delivering and reinserting the fetal extremity by gentle traction on the suture ends of the uterine pouch. 3. The use of the greater saphenous vein instead of the artery. 4. The use of citrated blood instead of heparinized blood. 5. The closure of the amniotic sac in a purse string fashion. We used the vein instead of the artery in order to avoid arterial circulatory disturbances. Citrated blood, although lowering the pH, was preferred over heparinized blood, so as to decrease unwarranted fetal bleeding.
REFERENCES
1. Adamsons, K., Jr., Freda, V. F., James, L. S. and Towell, M. E.: Pediatrics 35: 848, 1965. 2. Allen, F. H ., and Diamond, L. K. : New England J. Med . 257: 761, 1957. 3. Bevis, D . C. A.: Lancet 1: 395, 1952. 4. Crosby, W. M., and Merrill, J. A.: AM. J. OBST. & GVNEC. 92: 53, 1965. 5. Eriksson, G., and Wiqvist, N.: AM. J. OBST. & GVNEC. 91: 1076, 1965. 6. Fairweather, D. V. I., and Walker, W.: J. Obst. & Gynaec. Brit. Comm. 71: 48, 1964. 7. Freda, V. J., and Adamsons, K., Jr.: AM. J. OBST. & GVNEC. 89: 817, 1964. 8. Freda, V. J., and Gorman, J. G.: Bull. Sloane Hosp. Women 8: 147, 1962.
Intrauterine exchange transfusion
1133
The ammotlc sac was closed in a purse string fashion. On microscopic examination of the suture line there was no histologic evidence of fibrosis or scar formation, even in the area of the amniotic sac still containing a suture. Cultures taken from amniotic fluid, uterine cavity, umbilical cord, fetal skin, fetal gastric contents, and blood exchanged were negative. Blood samples for pH, pC0 2 , and p02 were periodically obtained during the intrauterine exchange procedure but technical difficulties with the instruments prevented the analysis of such data. The absence of premature labor, the minimal trauma sustained by the fetus, and the relatively long-term correction of the anemia have Jed us to believe that this procedure might be the safest and the one that can provide most definite treatment for the severely affected erythroblastotic fetuses. Further knowledge of human fetal physiology is, however, necessary, to widen the scope of this rather promising field of research and treatment. Weare deeply in debt to Drs. H. Rodriguez de Curet, N. de Jesus, A. Martinez Pico, and L. Diaz Bonet, S. Kaye, and to Mr. J. Perez for their assistance and help.
9. Freda, V. J.: AM. J. OBST. & GVNEC. 92: 341, 1965. 10. Liley, A. W.: AM. J. OBST. & GVNEC. 82: 1359, 1961. 11. Liley, A. W.: AM. J. OBST. & GVNEC. 86: 845, 1963. 12. Liley, A. W.: Brit. M . J. 2: 1107, 1963. 13. Liley, A. W.: Pediatrics 35: 836, 1965. 14. Liley, A. W.: Amniocentesis and amniography in hemolytic disease. Year Book of Obstetrics and Gynecology, Chicago, 1964, Year Book Medical Publishers. 15. Walker, A. H. C.: Brit. M. J. 2: 376, 1957.