AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 8, NUMBER 3
May 1991
PLEURAL EFFUSION IN ANEUPLOIDY Boris M. Petrikovsky, M.D., Ph.D., Susan M. Shmoys, M.D., David A. Baker, M.D., and Alan G. Monheit, M.D.
ABSTRACT
Fetal pleural effusion is a rare but significant abnormality. The following findings were described in association with pleural effusion: generalized hydrops fetalis, congenital pulmonary lymphangiectasis, tracheoesophageal fistula, extralobar sequestrated lung, and cardiac anomalies.1-2 The presence of a pleural effusion does not traditionally put the fetus in a high-risk category for chromosomal abnormalities. Review of the literature revealed only two cases of isolated pleural effusion in infants with Down and Turner syndromes reported earlier from our institution.2 The purpose of this communication is to report three consecutive cases of pleural effusion and fetal aneuploidy, including one with trisomy 13. Prenatally detected pleural effusion, to our knowledge, has not previously been described in a fetus with trisomy 13.
The only abnormal finding during this examination was mild pericardial effusion. Fetal echocardiography revealed normal results. The follow-up ultrasound examination revealed a mild right-sided pleural effusion. The third ultrasound performed at 26 weeks of pregnancy was significant for massive bilateral pleural effusion (Fig. 1). A genetic amniocentesis was performed prior to performing pleuroamniotic shunting, the results of which revealed 4 7 XX + 13. The patient subsequently delivered a stillborn female fetus with small wideset eyes, polydactaly, and deformed ears. The patient refused autopsy. Microscopic examination of the placenta revealed mild fibrin deposition. Umbilical cord had three blood vessels. Case 2
CASE REPORTS
Case 1
A 29-year-old white woman, gravida 3, para 1, was referred to our institution at 25 weeks' gestation for evaluation of "irregular" fetal heart tones. Ultrasound examination in our perinatal unit revealed a singleton fetus in a vertex presentation. The placenta was anterior and grade 1; the amniotic fluid volume was normal, the biparietal diameter (BPD), head circumference, femur length, and abdominal circumference were all compatible with 24 weeks' gestation.
A 34-year-old white woman, gravida 4, para 1, was referred to our institution at 34 weeks' gestation for assessment of fetal growth. Previous ultrasound examination performed at 26 weeks of pregnancy revealed no abnormalities. Repeat ultrasound examination at our perinatal unit revealed a singleton fetus, at approximately 34 weeks of gestation, in a vertex presentation with anterior grade I placenta and normal amount of amniotic fluid. The only abnormal finding was a bilateral pleural effusion. An amniocentesis was performed and a fetal lung maturity established, based on an lecithin to sphingomyelin (L/S) ratio. The decision was made to induce labor and treat the pleural effusion ex utero. The patient had a normal spontaneous vagi-
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, State University of New York at Stony Brook, Stony Brook, New York Reprint requests: Dr. Petrikovsky, Maternal and Fetal Medicine, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794-8091
214
Copyright © 1991 by Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
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Three consecutive cases of isolated pleural effusion in aneuploid fetuses are reported. The presence of pleural effusion in trisomy 13 had not been described in the literature previously. Early development of pleural effusion is usually associated with fetal hydrops and carries a poor prognosis. Late development of pleural effusion can be treated in utero. A karyotype should be performed in all cases of pleural effusion prior to in utero pleuroamniotic shunting.
Figure 1. Massive pleural effusion in the fetus with trisomy 13.
nal delivery. The neonate had stigmata of Down syndrome. A radiograph performed in the early neonatal period was diagnostic for bilateral pleural effusion, which were treated surgically. Fetal blood karyotyping confirmed trisomy 21. Case 3
A 34-year-old white woman, gravida 3, para 1, was referred to our institution for evaluation of an abnormal ultrasound performed for dating purposes. The pregnancy was at approximately 18 weeks' gestation with BPD, femur length, and head circumference within 2 standard deviations of dates. The ultrasound evaluation was remarkable for bilateral massive pleural effusion. The patient refused amniocentesis and had a termination of pregnancy. Karyotyping performed on placental tissue revealed a 47XX, +21. Gross examination of the fetus revealed clinodactyly of the 5th digits, simian creases, and a large space between the 4th and 5th digits. The results of the autopsy were significant for dilated lymphatics in the subcuteneous tissue and lungs and superficial calcifications in the liver. DISCUSSION
There is a wide body of literature that documents the association of aneuploidy and fetal hy-
drops. Turner's syndrome is the most common among the chromosomal abnormalities associated with hydrops.4 The excessive fluid in Turner syndrome could be confined to the fetal neck (cystic hygroma), extremities, or be diffuse. Nonimmune hydrops was also described in the fetuses with trisomies 13, 18, and 21 as well as in triploidy.5-7 Combination of pleural effusion and hydrops fetalis can present some clues to the etiology of the latter. Thus, fetuses without anemia as a cause of hydrops have pleural effusions in 87% and marked edema in 62.5%.8 Those with anemia as a cause of hydrops exhibit pleural effusions only in 20% and marked edema in 10%.8 In our series, however, we dealt with isolated pleural effusions without hydrops fetalis or prior to its subsequent development. The observed association of isolated fetal pleural effusion and chromosomal abnormalities warrants attention from both practical and theoretical points of view. From a practical standpoint, prenatally diagnosed fetal pleural effusion can be successfully treated in utero with pleuroamniotic shunting.9 The authors observed the resolution of polyhydramnios and the fetal hydrops within 1 week of shunting in all cases. The documented association of pleural effusion and aneuploidy should serve as an indication for fetal karyotyping prior to the decision to perform in utero intervention. Failure to do so may result in operating on the fetus with aneuploidy.10 The association of fetal pleural effusion and trisomy may shed some light on the etiology and natural history of the former. A pleural effusion can either be a part of fetal hydrops or present as an isolated abnormality. When pleural effusion is a component of hydrops, it usually appears in the first or early second trimester of pregnancy and generally carries a poor prognosis. Early lymphatic distention prior to the formation of the muscular layer in major fetal vessels is likely to cause hydrops fetalis by altering aortic and pulmonary bloodflow,thereby predisposing to compression of the aorta.11 Isolated pleural effusion can also be detected in the late second and third trimesters of pregnancy. Lymphatic distention in a more mature fetus does not affect aortic blood flow but may increase the splanchnic space between the developing lung and pericardium, thereby causing the pleural effusion. In summary, it appears that pleural effusion progressing to hydrops can be a part of any aneuploidy, thereby making karyotyping an essential part of the evaluation. In addition, when a pleural effusion occurs early in pregnancy, the fetus must be monitored for progression to generalized hydrops. Isolated pleural effusion should also be included among the clinical manifestations of trisomy 13. REFERENCES Romero R, Pilo G, Jeanty P, et al: Prenatal Diagnosis of Congenital Anomalies. Norwalk, CT: Appleton & Lange, 1988, pp 195-198 215
Downloaded by: Universite Laval. Copyrighted material.
PLEURAL EFFUSION IN ANEUPLOIDY/Petrikovsky, et al.
AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 8, NUMBER 3
2. Jouppila P. Kirkinen P, Herva R, et al: Prenatal diagnosis of pleural effusions by ultrasound. JCU 11:516-519, 1983 3. Yoss BS, Lipsitz PJ: Chylothorax in two mongoloid infants. Clin Genet 12:357-360, 1977 4. Romero R, CopelJ, Jeanty P, HobbinsJ: Causes, diagnosis and management of non-immune hydrops fetalis. In: Clinics in Diagnostic Ultrasound. New York: Churchill Liv-
col 38:86, 1971 8. Saltzman DH, Frigoletto FD, Harlow BL, et al: Sonographic evaluation of hydrops fetalis. Obstet Gynecol 74:106, 1989 9. Blott M, Nicolaides KH, Greenough A: Pleuroamniotic shunting for decompression of fetal pleural effusions. Obstet Gynecol 71:798-800, 1988 10. Rodeck CH, Fisk NM, Fraser DI, Nicolini U: Long-term inutero drainage of fetal hydrothorax. N Engl J Med 10: 1135-1138, 1988 11. Lacro RV, Jones KL, Benirschke K: Coarctation of the aorta in Turner syndrome: A pathologic study of fetuses with nuchal cystic hygromas, hydrops fetalis, and female genitalia. Pediatrics 444-451, 1988
Downloaded by: Universite Laval. Copyrighted material.
ingstone, 1986, pp 31-52 5. Macafee CAJ, Fortune DW, Beischer NA: Non-immunological hydrops fetalis. J Obstet Gynaecol Br Commonw 77:226,1970 6. Davis CL: Diagnosis and management of nonimmune hydrops fetalis. J Reprod Med 27:594, 1982 7. Beisher NA, Fortune DW, Macafee J: Nonimmunologic hydrops fetalis and congenital abnormalities. Obstet Gyne-
May 1991
216
May 1991
PLEURAL EFFUSION IN ANEUPLOIDY Boris M. Petrikovsky, M.D., Ph.D., Susan M. Shmoys, M.D., David A. Baker, M.D., and Alan G. Monheit, M.D.
ABSTRACT
Fetal pleural effusion is a rare but significant abnormality. The following findings were described in association with pleural effusion: generalized hydrops fetalis, congenital pulmonary lymphangiectasis, tracheoesophageal fistula, extralobar sequestrated lung, and cardiac anomalies.1-2 The presence of a pleural effusion does not traditionally put the fetus in a high-risk category for chromosomal abnormalities. Review of the literature revealed only two cases of isolated pleural effusion in infants with Down and Turner syndromes reported earlier from our institution.2 The purpose of this communication is to report three consecutive cases of pleural effusion and fetal aneuploidy, including one with trisomy 13. Prenatally detected pleural effusion, to our knowledge, has not previously been described in a fetus with trisomy 13.
The only abnormal finding during this examination was mild pericardial effusion. Fetal echocardiography revealed normal results. The follow-up ultrasound examination revealed a mild right-sided pleural effusion. The third ultrasound performed at 26 weeks of pregnancy was significant for massive bilateral pleural effusion (Fig. 1). A genetic amniocentesis was performed prior to performing pleuroamniotic shunting, the results of which revealed 4 7 XX + 13. The patient subsequently delivered a stillborn female fetus with small wideset eyes, polydactaly, and deformed ears. The patient refused autopsy. Microscopic examination of the placenta revealed mild fibrin deposition. Umbilical cord had three blood vessels. Case 2
CASE REPORTS
Case 1
A 29-year-old white woman, gravida 3, para 1, was referred to our institution at 25 weeks' gestation for evaluation of "irregular" fetal heart tones. Ultrasound examination in our perinatal unit revealed a singleton fetus in a vertex presentation. The placenta was anterior and grade 1; the amniotic fluid volume was normal, the biparietal diameter (BPD), head circumference, femur length, and abdominal circumference were all compatible with 24 weeks' gestation.
A 34-year-old white woman, gravida 4, para 1, was referred to our institution at 34 weeks' gestation for assessment of fetal growth. Previous ultrasound examination performed at 26 weeks of pregnancy revealed no abnormalities. Repeat ultrasound examination at our perinatal unit revealed a singleton fetus, at approximately 34 weeks of gestation, in a vertex presentation with anterior grade I placenta and normal amount of amniotic fluid. The only abnormal finding was a bilateral pleural effusion. An amniocentesis was performed and a fetal lung maturity established, based on an lecithin to sphingomyelin (L/S) ratio. The decision was made to induce labor and treat the pleural effusion ex utero. The patient had a normal spontaneous vagi-
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, State University of New York at Stony Brook, Stony Brook, New York Reprint requests: Dr. Petrikovsky, Maternal and Fetal Medicine, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794-8091
214
Copyright © 1991 by Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
Downloaded by: Universite Laval. Copyrighted material.
Three consecutive cases of isolated pleural effusion in aneuploid fetuses are reported. The presence of pleural effusion in trisomy 13 had not been described in the literature previously. Early development of pleural effusion is usually associated with fetal hydrops and carries a poor prognosis. Late development of pleural effusion can be treated in utero. A karyotype should be performed in all cases of pleural effusion prior to in utero pleuroamniotic shunting.
Figure 1. Massive pleural effusion in the fetus with trisomy 13.
nal delivery. The neonate had stigmata of Down syndrome. A radiograph performed in the early neonatal period was diagnostic for bilateral pleural effusion, which were treated surgically. Fetal blood karyotyping confirmed trisomy 21. Case 3
A 34-year-old white woman, gravida 3, para 1, was referred to our institution for evaluation of an abnormal ultrasound performed for dating purposes. The pregnancy was at approximately 18 weeks' gestation with BPD, femur length, and head circumference within 2 standard deviations of dates. The ultrasound evaluation was remarkable for bilateral massive pleural effusion. The patient refused amniocentesis and had a termination of pregnancy. Karyotyping performed on placental tissue revealed a 47XX, +21. Gross examination of the fetus revealed clinodactyly of the 5th digits, simian creases, and a large space between the 4th and 5th digits. The results of the autopsy were significant for dilated lymphatics in the subcuteneous tissue and lungs and superficial calcifications in the liver. DISCUSSION
There is a wide body of literature that documents the association of aneuploidy and fetal hy-
drops. Turner's syndrome is the most common among the chromosomal abnormalities associated with hydrops.4 The excessive fluid in Turner syndrome could be confined to the fetal neck (cystic hygroma), extremities, or be diffuse. Nonimmune hydrops was also described in the fetuses with trisomies 13, 18, and 21 as well as in triploidy.5-7 Combination of pleural effusion and hydrops fetalis can present some clues to the etiology of the latter. Thus, fetuses without anemia as a cause of hydrops have pleural effusions in 87% and marked edema in 62.5%.8 Those with anemia as a cause of hydrops exhibit pleural effusions only in 20% and marked edema in 10%.8 In our series, however, we dealt with isolated pleural effusions without hydrops fetalis or prior to its subsequent development. The observed association of isolated fetal pleural effusion and chromosomal abnormalities warrants attention from both practical and theoretical points of view. From a practical standpoint, prenatally diagnosed fetal pleural effusion can be successfully treated in utero with pleuroamniotic shunting.9 The authors observed the resolution of polyhydramnios and the fetal hydrops within 1 week of shunting in all cases. The documented association of pleural effusion and aneuploidy should serve as an indication for fetal karyotyping prior to the decision to perform in utero intervention. Failure to do so may result in operating on the fetus with aneuploidy.10 The association of fetal pleural effusion and trisomy may shed some light on the etiology and natural history of the former. A pleural effusion can either be a part of fetal hydrops or present as an isolated abnormality. When pleural effusion is a component of hydrops, it usually appears in the first or early second trimester of pregnancy and generally carries a poor prognosis. Early lymphatic distention prior to the formation of the muscular layer in major fetal vessels is likely to cause hydrops fetalis by altering aortic and pulmonary bloodflow,thereby predisposing to compression of the aorta.11 Isolated pleural effusion can also be detected in the late second and third trimesters of pregnancy. Lymphatic distention in a more mature fetus does not affect aortic blood flow but may increase the splanchnic space between the developing lung and pericardium, thereby causing the pleural effusion. In summary, it appears that pleural effusion progressing to hydrops can be a part of any aneuploidy, thereby making karyotyping an essential part of the evaluation. In addition, when a pleural effusion occurs early in pregnancy, the fetus must be monitored for progression to generalized hydrops. Isolated pleural effusion should also be included among the clinical manifestations of trisomy 13. REFERENCES Romero R, Pilo G, Jeanty P, et al: Prenatal Diagnosis of Congenital Anomalies. Norwalk, CT: Appleton & Lange, 1988, pp 195-198 215
Downloaded by: Universite Laval. Copyrighted material.
PLEURAL EFFUSION IN ANEUPLOIDY/Petrikovsky, et al.
AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 8, NUMBER 3
2. Jouppila P. Kirkinen P, Herva R, et al: Prenatal diagnosis of pleural effusions by ultrasound. JCU 11:516-519, 1983 3. Yoss BS, Lipsitz PJ: Chylothorax in two mongoloid infants. Clin Genet 12:357-360, 1977 4. Romero R, CopelJ, Jeanty P, HobbinsJ: Causes, diagnosis and management of non-immune hydrops fetalis. In: Clinics in Diagnostic Ultrasound. New York: Churchill Liv-
col 38:86, 1971 8. Saltzman DH, Frigoletto FD, Harlow BL, et al: Sonographic evaluation of hydrops fetalis. Obstet Gynecol 74:106, 1989 9. Blott M, Nicolaides KH, Greenough A: Pleuroamniotic shunting for decompression of fetal pleural effusions. Obstet Gynecol 71:798-800, 1988 10. Rodeck CH, Fisk NM, Fraser DI, Nicolini U: Long-term inutero drainage of fetal hydrothorax. N Engl J Med 10: 1135-1138, 1988 11. Lacro RV, Jones KL, Benirschke K: Coarctation of the aorta in Turner syndrome: A pathologic study of fetuses with nuchal cystic hygromas, hydrops fetalis, and female genitalia. Pediatrics 444-451, 1988
Downloaded by: Universite Laval. Copyrighted material.
ingstone, 1986, pp 31-52 5. Macafee CAJ, Fortune DW, Beischer NA: Non-immunological hydrops fetalis. J Obstet Gynaecol Br Commonw 77:226,1970 6. Davis CL: Diagnosis and management of nonimmune hydrops fetalis. J Reprod Med 27:594, 1982 7. Beisher NA, Fortune DW, Macafee J: Nonimmunologic hydrops fetalis and congenital abnormalities. Obstet Gyne-
May 1991
216
