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Fetal transfusion syndrome: Antenatal factors predicting outcome
Fetal transfusion syndrome: Antenatal factors predicting outcome Michael W. Bebbington, MD, and Bernd K. Wittmann, MD Vancouver, British Columbia, Canada Fetal transfusion syndrome is a serious complication of monozygotic multiple pregnancy and is associated with a high perinatal mortality rate. Recent literature has outlined aggressive interventions that attempt to improve the outcome of these pregnancies. We identified 25 cases of fetal transfusion syndrome from 595 multiple pregnancies delivered between January 1983 and December 1987 at the Grace Hospital. Analysis of antenatal factors with respect to survival showed that gestational age at delivery, the presence of hydrops, and the use of decompression amniocentesis may help in predicting outcome. These factors may be useful in deciding on the appropriate therapeutic approach for a particular pregnancy. (AM J OesTET GVNECOL 1989;160:913-5.)
Key words: Twins, triplets, fetal transfusion syndrome, antenatal management
Fetal transfusion syndrome represents a serious complication affecting monozygous multiple pregnancies with monochorial placentation. It is estimated that up to 85% of monochorial placentas have vascular anastomoses that allow for the transfer of blood between fetuses: however, only 5% to 10% of these will show sufficient imbalance to produce a fetal transfusion syndrome.' In these pregnancies the perinatal mortality rate is upward of 70%; usually from the sequelae of circulatory overload in the recipient or exsanguination of the donor. Recently, aggressive and invasive procedures, such as selective feticide, placental vessel punctures, and the use of digoxin, that attempt to improve the outcome of pregnancies affected by fetal transfusion syndrome have been reported.' Such procedures, even if successful, raise serious and as yet unresolved, ethical dilemmas. Not all affected pregnancies require these types of interventions and thus their global application is unwarranted. This study was undertaken to determine if antenatal factors can be used to identify those pregnancies where more aggressive management may be indicated to improve outcome.
Material and methods A retrospective review was undertaken of 598 multiple pregnancies between January 1983 and December From the DivisIOn of Maternal-Fetal Medlcme, Department of Obstetnes and Gynecology, Salvation Army Grace Hospital, U mverslty of BritISh Columbia. Presented at the Fortyfourth Annual Meeting of The SOflf(V of ObstetnClans and Gynaecologtsts of Canada, Vancouver, BntlSh Columbia, Canada, june 21-25,1988. Repnnt reque5ts: M. W. Bebblngton, MD, Depm'tment of Obstetrics and Gynecology, Umversity of BntlSh Columbia, Grace HOSpital, 4490 Oak St., Vancouver, Bn/ish Columbia, Canada V6H 3V5.
1987 at the Grace Hospital in Vancouver. Placental abnormalities were detected in approximately 95% of cases. There were 34 cases of monochorial placentas and vascular anastomoses. Nine cases were excluded from analysis because the abnormalities were diagnosed post partum, after routine pathologic examination. None of these nine cases demonstrated any manifestations of fetal transfusion syndrome. Antenatally this was defined clinically by the development of acute hydramnios in the second trimester or by ultrasonographic criteria (Table I). In the neonatal period a difference in weight of at least 20%,' a difference in hemoglobin of at least 50 gm/L,' or the presence of hydrops in the recipient was used to diagnose fetal transfusion syndrome. All of the remaining 25 cases were diagnosed by ultrasonography, and at least two of the five ultrasonographic criteria for the diagnosis of fetal transfusion syndrome were present (Table I). Survival through the neonatal period was used to divide these cases into two groups. Comparison was made for the antenatal factors listed in Table II. Statistical analysis was done with an unpaired, two-tailed t test or Fisher's exact test.
Results A total of 51 infants were delivered in the 25 cases analyzed (24 twin pregnancies, 1 triplet pregnancy). The mean gestational age at the time of diagnosis for the group was 22.3 ± 5.6 weeks (range 14 to 35 weeks). The mean gestational age at the time of delivery was 28.3 ± 5.6 weeks (range 21 to 38 weeks), and the mean interval between diagnosis and delivery was 6 ± 6.3 weeks. Of the 51 infants, 21 (41 o/c) survived past the end of the neonatal period, there were 9 stillbirths and 21 neonatal deaths. There was no statistical difference 913
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Bebbington and Wittmann
Table I. Ultrasonographic criteria for the diagnosis of fetal transfusion syndrome* I. Significant disparity in size with fetuses of same sex 2. Disparity in size between two amniotic sacs 3. Two separate umbilical cords with disparity in size or number of vessels 4. Single placenta with areas of disparity in echogenicity of cotyledons supplying two cords 5. Evidence of hydrops in eigher fetus or findings of congestive cardiac failure in the recipient *Modified from BrennanJN, Divan RV, Mortimer GR, Bellon EM. Radiology 1982;143:535-6.
between the groups of survivors and perinatal deaths when compared for maternal age, parity, method of diagnosis, reasons for delivery, or use of conservative management. The earliest gestational age for survival was 28 weeks. None of the infants born with hydrops survived the neonatal period regardless of the gestational age at delivery. Similarly, in pregnancies where decompression amniocentesis was required to relieve maternal respiratory compromise, there were no surviving infants. Predictors for survival included a later gestational age at the time of diagnosis of fetal transfusion syndrome and a later gestational age at the time of delivery. These findings are summarized in Table III.
Comment Fetal transfusion syndrome results from imbalanced transplacental arteriovenous communications. A spectrum of clinical severity exists in relation to the size and number of anastomoses and the flow patterns in the areas of shunting. The shunt may be so minor that it has no obvious effect on intrauterine development, or it may be so severe that the donor develops growth retardation, anemia, and oligohydramnios while the recipient becomes hydropic with visceromegaly, polycythemia, and polyhydramnios. The syndrome usually becomes clinically apparent in the second trimester as a result of the development of acute hydramnios caused by increased fetal urination, which is due to the intravascular volume overload in the recipient. Maternal discomfort and respiratory embarrassment, premature rupture of the membranes, preterm labor, and delivery of compromised, premature infants are the usual sequelae. A uniform management of fetal transfusion syndrome has not been published or agreed on. Conservative management in the past has consisted of bed rest and the use of tocolytics. Neither of these has been successful in improving outcomes. Weir et al. b reported one of the largest series in the literature involving eight patients with acute polyhydramnios secondary to monozygous twin pregnancies. Conservative
April 1989
Am
J Obstet Gynecol
Table II. Antenatal factors used for comparison I. 2. 3. 4. 5.
Parity Method of diagnosis-ultrasonography Use of conservative management Use of decompression amniocentesis Reason for delivery Intrauterine death Preterm labor Spontaneous rupture of membranes Fetal distress Intrauterine growth retardation Other (i.e., pregnancy-induced hypertension) 6. Gestational age at delivery 7. Interval between diagnosis and delivery
therapy resulted in 100% perinatal mortality. Since first reported by Erskin 7 in 1944, amniocentesis has been used to treat the acute hydramnios that accompanies severely affected pregnancies. Several small series have been reported,· but the outcome is generally poor with little prolongation of the pregnancy. Benirschke and Driscoll" first suggested surgical treatment by ligation of one of the umbilical cords in severe cases where poor outcome was inevitable. Successful medical management of cardiac failure in the recipient twin has been reported in one case.1O More recently, Wittmann et aJ.3 have reported the use of selective feticide in the management of severe fetal transfusion syndrome. Vetter and Schneiderll have reported successful outcomes in two affected pregnancies after unintentional puncture of a placental vessel. The actual incidence of fetal transfusion syndrome is unknown, but our incidence of 5.6% of multiple pregnancies is consistent with that reported by others. lO • 12 Results from this study reinforce the opinion that decompression amniocentesis adds nothing to the management of fetal transfusion syndrome. The amniotic fluid reaccumulates rapidly because the pathophysiologic basis for the hydramnios is unchanged. Risk of infection, premature rupture of the membranes, premature labor, and abruptio placentae increase with repeated amniocenteses. Those pregnancies where the hydramnios reaches proportions requiring amniocentesis for symptomatic relief are likely among the most severely affected. Delivery in this subgroup occurred at a mean gestational age of 25.5 weeks compared with 28.5 weeks for the group as a whole (p = 0.1). The fact that there were no survivors from the pregnancies where decompression amniocentesis was performed likely reflects this difference in gestational age at delivery. Those fetuses that develop hydrops obviously have the most severe form of the syndrome. Many die in utero, but even if they are alive at birth, hydropic babies have a high neonatal mortality rate. This is true
Fetal transfusion syndrome
Volume 160 Number 4
915
Table III. Antenatal factors predicting outcome Antenatal factor
SurvIVors
Deaths
p Value
Gestational age at diagnosis (wk) Gestational age at delivery (wk) Presence of hydrops Decompression amniocentesis
252 ± 6.6 32.7 ± 3.4
20.3 ± 3.7 25.7 ± 4 5 6
0.01 0.001 0.05 0.05
o o
even when they are born at a more advanced gestational age. In our series the gestational age at the time of delivery for hydropic infants ranged from 24 to 32 weeks. Our study shows that a good pregnancy outcome is best predicted by a more advanced gestational age at the time of clinical presentation and more importantly an advanced gestational age at the time of delivery. Early gestational age at diagnosis (20 ± 3 weeks), early gestational age at delivery (25 ± 4 weeks), the presence or development of hydrops, and the need to use decompression amniocentesis to relieve maternal symptoms are all predictors of poor perinatal outcome. The latter two factors reflect the most severe aspects of the syndrome. The watershed for survival would appear to be 28 weeks' gestation. Of the 22 infants born after 28 weeks, 17 survived. This gives an overall survival rate of 77% in this subgroup, compared with 41 % for the group as a whole. Of the five who died after 28 weeks, three died for reasons not directly related to fetal transfusion syndrome. This would suggest that if fetal transfusion syndrome is diagnosed around 28 weeks' gestation and hydrops is not present, then conservative treatment may be all that is warranted. However, if the diagnosis is made well before the 28-week mark, if hydrops is present, or if decompression amniocentesis is required, then consideration should be given to other, more aggressive modes of intervention. REFERENCES l. Newton ER. Antepartum care Semin PerinatoI1986;10:19-29.
In
multiple gestation.
2. Brennan ]N, Diwan RV, Mortimer GR, Bellon EM. Fetofetal transfusion syndrome: prenatal ultrasonographic diagnosis. Radiology 1982; 143:535-6. 3. Wittmann BK, Farquharson DF, Thomas WDS. Baldwin V], Wadsworth LD. The role of feticide in the management of severe twin transfusion syndrome. AM] OBS1'E1' GYNECOL 1986; 155: 1023-6. 4. Tan KL, Tan R. Tan SH, Tan AM. The twin transfusion syndrome. Clin Pediatr (Phila) 1979; 18: 111-4. 5. Galea P, Scott ]M, Goel KM. Feto fetal transfusion syndrome. Arch Dis Child 1982;57:781-3. 6. Weir PE, Ratten G]. Beischer NA. Acute polyhydramnios-a complication of monozygous twin pregnancy. Br ] Obstet Gynaecol 1979;86:849-53. 7. Erskin ]P. Amniocentesis in the treatment of polyhydramnios in a twin pregnancy. ] Obstet Gynaecol Br Emp 1944;51:549-5l. 8. Feingold M, Cetrulo CL, Newton ER, Weiss], Shakr C, Shmoys S. Serial amniocentesis in the treatment of twin to twin transfusion complicated by acute polyhydramnios. Acta Genet Med GemelloI1986;35:107-13. 9. Benirschke K, Driscoll SG. The pathology of the human placenta. New York: Springer-Verlag, 1967. 10. DeLia], Embery MG, Sheafor SA, Jennison TA. Twin transfusion syndrome: successful in utero treatment with digoxin. Int] Gynaecol Obstet 1985;23:197-201. 11. Vetter K, Schneider KTM. Iatrogenous remission of twin transfusion syndrome [Letter]. AM ] OBS1'E1' GYNECOL 1988;158:22l. 12. Robertson EG, Neer KJ. Placental injection studies in twin gestation. AM] OB5TET GYNECOL 1983; 147: 170-4. 13. Achiron R, Rosen N, Zakut H. Pathophysiologic mechanisms of hydramnios in twin transfusion syndrome.] Reprod Med 1987;32:305-8. 14. Wittmann BK, Baldwin V], Nicol B. Antenatal diagnosis of twin transfusion syndrome by ultrasound. Obstet GynecoI1981;58:123-7. 15. Barss VA, Benacerraf BR, Frigoletto FD. Ultrasonographic determination of chorion type In twin gestation. Obstet Gynecol 1985:66:779-82.
Key words: Twins, triplets, fetal transfusion syndrome, antenatal management
Fetal transfusion syndrome represents a serious complication affecting monozygous multiple pregnancies with monochorial placentation. It is estimated that up to 85% of monochorial placentas have vascular anastomoses that allow for the transfer of blood between fetuses: however, only 5% to 10% of these will show sufficient imbalance to produce a fetal transfusion syndrome.' In these pregnancies the perinatal mortality rate is upward of 70%; usually from the sequelae of circulatory overload in the recipient or exsanguination of the donor. Recently, aggressive and invasive procedures, such as selective feticide, placental vessel punctures, and the use of digoxin, that attempt to improve the outcome of pregnancies affected by fetal transfusion syndrome have been reported.' Such procedures, even if successful, raise serious and as yet unresolved, ethical dilemmas. Not all affected pregnancies require these types of interventions and thus their global application is unwarranted. This study was undertaken to determine if antenatal factors can be used to identify those pregnancies where more aggressive management may be indicated to improve outcome.
Material and methods A retrospective review was undertaken of 598 multiple pregnancies between January 1983 and December From the DivisIOn of Maternal-Fetal Medlcme, Department of Obstetnes and Gynecology, Salvation Army Grace Hospital, U mverslty of BritISh Columbia. Presented at the Fortyfourth Annual Meeting of The SOflf(V of ObstetnClans and Gynaecologtsts of Canada, Vancouver, BntlSh Columbia, Canada, june 21-25,1988. Repnnt reque5ts: M. W. Bebblngton, MD, Depm'tment of Obstetrics and Gynecology, Umversity of BntlSh Columbia, Grace HOSpital, 4490 Oak St., Vancouver, Bn/ish Columbia, Canada V6H 3V5.
1987 at the Grace Hospital in Vancouver. Placental abnormalities were detected in approximately 95% of cases. There were 34 cases of monochorial placentas and vascular anastomoses. Nine cases were excluded from analysis because the abnormalities were diagnosed post partum, after routine pathologic examination. None of these nine cases demonstrated any manifestations of fetal transfusion syndrome. Antenatally this was defined clinically by the development of acute hydramnios in the second trimester or by ultrasonographic criteria (Table I). In the neonatal period a difference in weight of at least 20%,' a difference in hemoglobin of at least 50 gm/L,' or the presence of hydrops in the recipient was used to diagnose fetal transfusion syndrome. All of the remaining 25 cases were diagnosed by ultrasonography, and at least two of the five ultrasonographic criteria for the diagnosis of fetal transfusion syndrome were present (Table I). Survival through the neonatal period was used to divide these cases into two groups. Comparison was made for the antenatal factors listed in Table II. Statistical analysis was done with an unpaired, two-tailed t test or Fisher's exact test.
Results A total of 51 infants were delivered in the 25 cases analyzed (24 twin pregnancies, 1 triplet pregnancy). The mean gestational age at the time of diagnosis for the group was 22.3 ± 5.6 weeks (range 14 to 35 weeks). The mean gestational age at the time of delivery was 28.3 ± 5.6 weeks (range 21 to 38 weeks), and the mean interval between diagnosis and delivery was 6 ± 6.3 weeks. Of the 51 infants, 21 (41 o/c) survived past the end of the neonatal period, there were 9 stillbirths and 21 neonatal deaths. There was no statistical difference 913
914
Bebbington and Wittmann
Table I. Ultrasonographic criteria for the diagnosis of fetal transfusion syndrome* I. Significant disparity in size with fetuses of same sex 2. Disparity in size between two amniotic sacs 3. Two separate umbilical cords with disparity in size or number of vessels 4. Single placenta with areas of disparity in echogenicity of cotyledons supplying two cords 5. Evidence of hydrops in eigher fetus or findings of congestive cardiac failure in the recipient *Modified from BrennanJN, Divan RV, Mortimer GR, Bellon EM. Radiology 1982;143:535-6.
between the groups of survivors and perinatal deaths when compared for maternal age, parity, method of diagnosis, reasons for delivery, or use of conservative management. The earliest gestational age for survival was 28 weeks. None of the infants born with hydrops survived the neonatal period regardless of the gestational age at delivery. Similarly, in pregnancies where decompression amniocentesis was required to relieve maternal respiratory compromise, there were no surviving infants. Predictors for survival included a later gestational age at the time of diagnosis of fetal transfusion syndrome and a later gestational age at the time of delivery. These findings are summarized in Table III.
Comment Fetal transfusion syndrome results from imbalanced transplacental arteriovenous communications. A spectrum of clinical severity exists in relation to the size and number of anastomoses and the flow patterns in the areas of shunting. The shunt may be so minor that it has no obvious effect on intrauterine development, or it may be so severe that the donor develops growth retardation, anemia, and oligohydramnios while the recipient becomes hydropic with visceromegaly, polycythemia, and polyhydramnios. The syndrome usually becomes clinically apparent in the second trimester as a result of the development of acute hydramnios caused by increased fetal urination, which is due to the intravascular volume overload in the recipient. Maternal discomfort and respiratory embarrassment, premature rupture of the membranes, preterm labor, and delivery of compromised, premature infants are the usual sequelae. A uniform management of fetal transfusion syndrome has not been published or agreed on. Conservative management in the past has consisted of bed rest and the use of tocolytics. Neither of these has been successful in improving outcomes. Weir et al. b reported one of the largest series in the literature involving eight patients with acute polyhydramnios secondary to monozygous twin pregnancies. Conservative
April 1989
Am
J Obstet Gynecol
Table II. Antenatal factors used for comparison I. 2. 3. 4. 5.
Parity Method of diagnosis-ultrasonography Use of conservative management Use of decompression amniocentesis Reason for delivery Intrauterine death Preterm labor Spontaneous rupture of membranes Fetal distress Intrauterine growth retardation Other (i.e., pregnancy-induced hypertension) 6. Gestational age at delivery 7. Interval between diagnosis and delivery
therapy resulted in 100% perinatal mortality. Since first reported by Erskin 7 in 1944, amniocentesis has been used to treat the acute hydramnios that accompanies severely affected pregnancies. Several small series have been reported,· but the outcome is generally poor with little prolongation of the pregnancy. Benirschke and Driscoll" first suggested surgical treatment by ligation of one of the umbilical cords in severe cases where poor outcome was inevitable. Successful medical management of cardiac failure in the recipient twin has been reported in one case.1O More recently, Wittmann et aJ.3 have reported the use of selective feticide in the management of severe fetal transfusion syndrome. Vetter and Schneiderll have reported successful outcomes in two affected pregnancies after unintentional puncture of a placental vessel. The actual incidence of fetal transfusion syndrome is unknown, but our incidence of 5.6% of multiple pregnancies is consistent with that reported by others. lO • 12 Results from this study reinforce the opinion that decompression amniocentesis adds nothing to the management of fetal transfusion syndrome. The amniotic fluid reaccumulates rapidly because the pathophysiologic basis for the hydramnios is unchanged. Risk of infection, premature rupture of the membranes, premature labor, and abruptio placentae increase with repeated amniocenteses. Those pregnancies where the hydramnios reaches proportions requiring amniocentesis for symptomatic relief are likely among the most severely affected. Delivery in this subgroup occurred at a mean gestational age of 25.5 weeks compared with 28.5 weeks for the group as a whole (p = 0.1). The fact that there were no survivors from the pregnancies where decompression amniocentesis was performed likely reflects this difference in gestational age at delivery. Those fetuses that develop hydrops obviously have the most severe form of the syndrome. Many die in utero, but even if they are alive at birth, hydropic babies have a high neonatal mortality rate. This is true
Fetal transfusion syndrome
Volume 160 Number 4
915
Table III. Antenatal factors predicting outcome Antenatal factor
SurvIVors
Deaths
p Value
Gestational age at diagnosis (wk) Gestational age at delivery (wk) Presence of hydrops Decompression amniocentesis
252 ± 6.6 32.7 ± 3.4
20.3 ± 3.7 25.7 ± 4 5 6
0.01 0.001 0.05 0.05
o o
even when they are born at a more advanced gestational age. In our series the gestational age at the time of delivery for hydropic infants ranged from 24 to 32 weeks. Our study shows that a good pregnancy outcome is best predicted by a more advanced gestational age at the time of clinical presentation and more importantly an advanced gestational age at the time of delivery. Early gestational age at diagnosis (20 ± 3 weeks), early gestational age at delivery (25 ± 4 weeks), the presence or development of hydrops, and the need to use decompression amniocentesis to relieve maternal symptoms are all predictors of poor perinatal outcome. The latter two factors reflect the most severe aspects of the syndrome. The watershed for survival would appear to be 28 weeks' gestation. Of the 22 infants born after 28 weeks, 17 survived. This gives an overall survival rate of 77% in this subgroup, compared with 41 % for the group as a whole. Of the five who died after 28 weeks, three died for reasons not directly related to fetal transfusion syndrome. This would suggest that if fetal transfusion syndrome is diagnosed around 28 weeks' gestation and hydrops is not present, then conservative treatment may be all that is warranted. However, if the diagnosis is made well before the 28-week mark, if hydrops is present, or if decompression amniocentesis is required, then consideration should be given to other, more aggressive modes of intervention. REFERENCES l. Newton ER. Antepartum care Semin PerinatoI1986;10:19-29.
In
multiple gestation.
2. Brennan ]N, Diwan RV, Mortimer GR, Bellon EM. Fetofetal transfusion syndrome: prenatal ultrasonographic diagnosis. Radiology 1982; 143:535-6. 3. Wittmann BK, Farquharson DF, Thomas WDS. Baldwin V], Wadsworth LD. The role of feticide in the management of severe twin transfusion syndrome. AM] OBS1'E1' GYNECOL 1986; 155: 1023-6. 4. Tan KL, Tan R. Tan SH, Tan AM. The twin transfusion syndrome. Clin Pediatr (Phila) 1979; 18: 111-4. 5. Galea P, Scott ]M, Goel KM. Feto fetal transfusion syndrome. Arch Dis Child 1982;57:781-3. 6. Weir PE, Ratten G]. Beischer NA. Acute polyhydramnios-a complication of monozygous twin pregnancy. Br ] Obstet Gynaecol 1979;86:849-53. 7. Erskin ]P. Amniocentesis in the treatment of polyhydramnios in a twin pregnancy. ] Obstet Gynaecol Br Emp 1944;51:549-5l. 8. Feingold M, Cetrulo CL, Newton ER, Weiss], Shakr C, Shmoys S. Serial amniocentesis in the treatment of twin to twin transfusion complicated by acute polyhydramnios. Acta Genet Med GemelloI1986;35:107-13. 9. Benirschke K, Driscoll SG. The pathology of the human placenta. New York: Springer-Verlag, 1967. 10. DeLia], Embery MG, Sheafor SA, Jennison TA. Twin transfusion syndrome: successful in utero treatment with digoxin. Int] Gynaecol Obstet 1985;23:197-201. 11. Vetter K, Schneider KTM. Iatrogenous remission of twin transfusion syndrome [Letter]. AM ] OBS1'E1' GYNECOL 1988;158:22l. 12. Robertson EG, Neer KJ. Placental injection studies in twin gestation. AM] OB5TET GYNECOL 1983; 147: 170-4. 13. Achiron R, Rosen N, Zakut H. Pathophysiologic mechanisms of hydramnios in twin transfusion syndrome.] Reprod Med 1987;32:305-8. 14. Wittmann BK, Baldwin V], Nicol B. Antenatal diagnosis of twin transfusion syndrome by ultrasound. Obstet GynecoI1981;58:123-7. 15. Barss VA, Benacerraf BR, Frigoletto FD. Ultrasonographic determination of chorion type In twin gestation. Obstet Gynecol 1985:66:779-82.