Hydrothorax

Hydrothorax is the accumulation of fluid in the pleural space. It can be primary or secondary, and unilateral or bilateral.

The incidence of hydrothorax is unknown. At diagnosis, it is bilateral in about 75% of the cases and is already associated with fetal hydrops in 60-65%.^{1, 2} If isolated, it is commonly due to congenital primary chylothorax, with an estimated incidence of 1/10.000-15.000 pregnancies.^{1, 2}  Prenatal diagnosis of hydrothorax was first reported in 1977.³

The etiology of congenital hydrothorax is highly variable. Antenatal primary hydrothorax typically corresponds to congenital chylothorax, and is mainly due to lymphatic leakage because of a malformation, atresia or fistula, in the development of pulmonary lymphatic vessels of the thoracic duct. This origin is, however, controversial, as there are few studies including histopathology to demonstrate it.²

Secondary hydrothorax is usually part of a generalized non-immune fetal hydrops, thus presenting with other fluid collections (ascites, skin edema, pericardial effusion), and its prognosis is mainly dependent on the underlying pathology.^{1, 2}

Primary fetal hydrothorax or congenital chylothorax is a diagnosis of exclusion and the workup is similar to that for hydrops. Excluding structural fetal malformations, especially cardiac anomalies and arrhythmias, is of high importance,^{4, 5} in particular pulmonary causes of secondary hydrothorax such as congenital cystic adenomatoid malformation, bronchopulmonary sequestration or congenital diaphragmatic hernia. Also, hydrothorax may be secondary to mediastinal tumors and congenital goiter. Congenital infections (TORCHES, parvovirus B19), fetomaternal hemorrhage and fetal anemia must be ruled out as well.^4-7

Chromosomal anomalies (mainly trisomy 21 and Turner syndrome) have been reported in up to 10-20% of the cases, particularly if the fetus is hydropic.^{4, 7-9} Even if the hydrothorax is isolated, it is diagnosed in the third trimester or it is transient, the risk of aneuploidy applies for at least 1-5%. An autosomal or X-linked recessive inheritance in some cases has been suggested. Also, there is an increased risk of non-chromosomal syndromes, especially if hydrops is associated, but in some instances, the hydrothorax may represent the only prenatally recognizable sign.^{4, 7-9}

Lastly, if the complete diagnostic work-up assessment is negative, the hydrothorax is classified as isolated and most likely as a congenital chylothorax. In such cases, the prognosis is better and the effusion may be even transitory, involuting spontaneously . ^{1, 2, 10}

The recurrence risk of hydrothorax depends on the underlying cause and the associated anomaly. In the case of isolated congenital chylothorax the recurrence risk is not known, but it should be very low.^{1, 2}

Prenatal diagnosis of congenital hydrothorax is based on the demonstration of fluid collection in the thorax, surrounding the lung uni or bilaterally, except for the hilium. It is usually diagnosed on the four-chamber view. If unilateral, it is considered as hypertensive if the intrathoracic pressure is high and the heart and all viscera are pushed into the contralateral hemithorax. If bilateral, it may produce increased venous return pressure and secondary hydrops.^{1, 2, 6, 10}

Regarding the etiologic diagnosis, an initial thoracocentesis is useful for diagnosing congenital chylothorax (more than 80% of lymphocytes in the blood count) and for decompressing the lungs.^{11, 12} Usually, this procedure alone will not resolve the problem, since in more than 70-80% of the cases the liquid will reaccumulate quickly.

Differential diagnosis with pericardial effusion is usually easy and straightforward, whenever the scan is performed by a medium experienced examiner. In pericardial effusion the fluid is surrounding the heart and both lungs remain attached to the posterior wall of the chest.

As aforementioned, the etiology of hydrothorax may be related to a potentially serious disease and primary congenital chylothorax is a diagnosis of exclusion. Thus, the workup should be the same to that for hydrops.^{2, 4} A thorough anatomic scan by an expert, in order to detect structural anomalies or signs possibly indicative of a syndromic context, and a complete echocardiographic evaluation to exclude cardiac structural or functional abnormalities are necessary. The ultrasound features can indicate the nature of the hydrothorax, since an isolated unilateral hydrothorax is more likely primary rather than secondary.^{2, 4}

Karyotyping and viral screening are mandatory, especially if a heart defect or other serous effusions (skin edema, pleural effusion, ascites) are detected, which would significantly increase the risk of chromosomal abnormalities.^4,7-9 Fetal karyotype can be obtained conventionally (amniocentesis, fetal blood sampling), but also by punction and aspiration of the pleural fluid with the same needle used for amniocentesis. This usually minimizes the invasive risk and expedites a full karyotype result,¹³ as almost invariably these effusions are replete with lymphocytes.^11-13 Kleihauer–Betke test to exclude fetomaternal hemorrhage and Doppler evaluation of the peak systolic velocity (PSV) in the middle cerebral artery to exclude fetal anemia should also be performed.

If all these investigations are normal, the hydrothorax is isolated and will probably be a congenital chylothorax, eventually being benign, even transitory, or, on the other hand, evolving to hydrops. In those cases, serial fetal scans must be performed in order to strictly follow-up until confirmation of the decrease and spontaneous resolution.^{2, 6, 14, 15} However, it can be difficult to differentiate between those fetuses in which the hydrops is secondary to a preceding effusion and those in whom the effusions are a feature of generalized hydrops.

The outlook of a fetus with hydrothorax mainly depends on the underlying cause, being the association with hydrops the most important prognostic factor. In these cases, the outcome is generally very poor, with a few exceptions. Congenital hydrothorax has highly variable clinical course and may regress, remain stable or worsen. In general, isolated chylothorax does appear to be associated with a better perinatal outcome and resolution, either spontaneously or after a single drainage, occurs in up to 10-25% of cases.¹⁵ However, it can also progress towards hydrops, pulmonary hypoplasia and perinatal death.^14-17 In the presence of hydrops, prenatal therapy improves the overall survival rate.

In general, survival ranges from 60-70% if hydrothorax is isolated to less than 10-20% if there is associated hydrops without treatment. Because of this poor prognosis and the uncertainty in follow-up, the option of pregnancy termination should be discussed with parents whenever the diagnosis of a pleural effusion with hydrops is made before viability.^{2, 6, 18}

After the diagnosis of fetal hydrothorax, the optimal antenatal management is controversial since some fetuses may not be significantly compromised, whereas others may develop hydrops or die at birth from pulmonary hypoplasia. Therefore, the decision to treat, deliver prematurely or follow conservatively can be difficult. In cases where there is rapid enlargement of the effusion on serial ultrasound or when hydrops or significant hydramnios develops, fetal therapy should be offered to decompress the fluid collection, to allow normal pulmonary development.^{6, 18} In addition, antenatal therapy can reverse hydrops and hydramnios and can facilitate neonatal ventilation.

a. - Conservative management

Primary fetal hydrothorax can resolve spontaneously in utero, thus conservative management is reasonable in cases with a primary (chromosomal anomalies and congenital infections have been ruled out), and small effusion, in the absence of significant mediastinal shift, hydrops or hydramnios.^{6, 15} The cases which opt for a conservative management warrant for a strict and very close follow-up. Serial ultrasounds will be performed weekly until resolution. In the case of spontaneous resolution, or if the effusion remains small, the prognosis is excellent without any intervention, with reported survival rates ranging from 75% to 100%.^{6, 19}

However, there are specific signs that suggest the presence of an elevated intrathoracic pressure and therefore an increased risk for developing hydrops. Some of these signs are enlargement of the pleural effusion, evident mediastinal shift, and increased cardiac preload (abnormal ductus venosus blood flow, tricuspid regurgitation, and cardiomegaly). Also hydramnios secondary to enlarged effusions causing esophageal compression and impeding fetal swallowing might lead to a poorer prognosis due to premature labor. The presence of any these markers, or the actual onset of hydrops, would be indications for urgent fetal intervention.^{18, 19}

b. - Antenatal thoracocentesis

Thoracocentesis to aspirate the pleural fluid was first proposed as a treatment of primary fetal hydrothorax in 1982.²⁰ It is performed under continuous ultrasound guidance using a 20-gauge needle inserted percutaneously. The main advantages of the technique are:

1. In up to 15-20% of the cases, short-term decompression disrupts the underlying pathology and the effusion does not recurr.^{6, 16}

2. Primary fetal chylothorax can be diagnosed by demonstrating a lymphocyte count of > 80% in pleural aspirate.^{11, 12}

3. A quick karyotype can be obtained from the aspirated lymphocytes.^11-13

4. Failure of the lungs to expand after decompression might suggest pulmonary hypoplasia.^{6, 17}

5. Associated anomalies, particularly an underlying cardiac or other intrathoracic anomaly, might become apparent only after decompression and return of the mediastinum to its normal position.^{18, 20}

6. Thoracocentesis just prior to delivery is encouraged to facilitate neonatal resuscitation.^{21, 22}

The main drawback of thoracocentesis is that in the majority of cases it is usually followed by rapid re-accumulation of the effusion within 24-48 hours, necessitating repeated taps. In such cases, the cumulative risk of them is very likely higher than that of a single pleuroamniotic shunt, which will provide effective ongoing drainage.^{6, 16}

c. - Pleuroamniotic shunting

The main goal in the management of a fetus with persistent hydrothorax is to drain the excess of fluid drainage, firstly, to permit an adequate lung expansion avoiding pulmonary hypoplasia, and, secondly, to reduce the risk of developing hydrops by diminishing intrathoracic pressure. As aforementioned, thoracocentesis, either unique or repeated, for drainage of pleural effusions are generally unsuccessful in reversing the hydropic state, because the fluid reaccumulates within 24-48 hours of drainage. A better approach is chronic drainage by the insertion of thoraco-amniotic shunts.^{6, 23}

This procedure was first proposed by Seeds and Bowes in 1986.²⁴ Nowadays, the technique we and most of the groups use for shunting is modified from that originally described by Rodeck et al.²⁵ Under continuous ultrasound guidance, a 3 mm trocar and cannula are introduced percutaneously into the amniotic cavity, and then advanced through the fetal chest wall into the effusion. The trocar is then removed and a double pigtail silastic catheter inserted to create a permanent communication between the pleural space and the amniotic cavity.

Approximately 10-20% of fetal shunts need to be replaced because of obstruction or other complications including catheter migration into the amniotic fluid, the fetal pleural space,^{6, 23, 26} or into the maternal peritoneal cavity.^{25, 27} In addition, shunting might cause preterm premature rupture of membranes in up to 10-15%, chorioamnionitis (1%), and preterm labor.²⁸ Prophylactic antibiotics and tocolysis are thus recommended for these procedures.

After shunt insertion, weekly ultrasound surveillance should be performed as, in cases of shunt failure, a repeat procedure might be warranted. Because of the significant decrease in survival with premature birth, we and others suggest to consider a shunt over delivery in any fetus at less than 36 weeks gestation.^{2, 6} If the initial diagnosis or worsening of the effusion occurs after 36 weeks gestation, thoracocentesis to improve the neonatal respiratory status followed by immediate delivery should be considered. In hydropic fetuses, even towards term, 24-48 hours of fluid equilibration following successful shunting can significantly improve the condition of the neonate, and neonatologists may rather prefer to receive babies whose birth has been precipitated as a result of shunting than babies who have had an elective delivery but who are sick hydropic neonates.^18-19

The outcome after shunting is dramatically influenced by the presence of hydrops, with perinatal survival of 70-100% in its absence compared to 45-65% survival in generalized hydropic fetuses.^{23, 25, 28-30} Though there are no randomized trials comparing pleuroamniotic shunting with thoracocentesis and/or conservative management, for hydropic fetuses with pleural effusions, data from larger series support invasive therapy, being pleuroamniotic shunting superior to thoracocentesis, while for non-hydropic fetuses the benefit of shunting is less clear.^2,6,18,19

d. - Pleurodesis

Recently, new forms of prenatal treatment of fetal hydrothorax have been described by intrapleural injection of OK-432,^31-35 which is derived from group A Streptococcus pyogenes of human origin and is used as a sclerosant for lymphangiomas in pediatric and adult patients. Also, the intrapleural injection of maternal blood has been successfully used in a couple of cases.³⁶ Since these procedures are not free of complications, further studies are needed to clarify their role as a reliable therapy.

Although the mode of delivery can be determined on normal obstetric grounds, more than 50% of the mothers deliver by caesarean section. If previously shunted, the chest drain should be clamped immediately after delivery to avoid development of a pneumothorax. Irrespective of the underlying cause, newborns may present with severe, even lethal, respiratory insufficiency, so delivery should occur at a third level center that can provide appropriate resuscitation, including chest-tube insertion, a full spectrum of ventilatory support (including high-frequency ventilation and ECMO) and management of fluid and nutrients.^{1, 2}

Postnatally, in most of the cases of primary chylothorax, resolution of the effusion occurs spontaneously with time, probably because collateral lymphatic channels develop. In some cases a special diet, even parenteral feeding may be needed, and if drainage remains persistent and copious, surgical ligation of the thoracic duct may be necessary. On the contrary, depending on the cause, no treatment may be possible for most cases of hydropic secondary hydrothorax.^{1, 2}

1. Longaker MT, Laberge JM, Dansereau J et al. Primary fetal hydrothorax: natural history and management. J Pediatr Surg 1989;24:573-576.

2. Yinon Y, Kelly E, Ryan G. Fetal pleural effusions. Best Practice and Research Clinical Obstetrics and Gynaecology 2008;22:77-96.

3. Carroll B. Pulmonary hypoplasia and pleural effusions associated with fetal death in utero: ultrasonic findings. Am J Roentgenol 1977;129:749-750.

4. Bellini C, Hennekam RC, Fulcheri E, Rutigliani M, Morcaldi G, Boccardo F, Bonioli E. Etiology of nonimmune hydrops fetalis: a systematic review. Am J Med Genet A. 2009;149A(5):844-851.

5. Beghetti M, La Scala G, Belli D, Bugmann P, Kalangos A, Le Coultre C. Etiology and management of pediatric chylothorax. J Pediatr 2000;136:653-8.

6. Aubard Y, Derouineau I, Aubard V, Chalifor V, Preux PM. Primary fetal hydrothorax: a literature review and proposed antenatal clinical strategy. Fetal Diagn Ther 1998;13:325-333.

7. Barron SD, Pass RF. Infectious causes of hydrops fetalis. Semin Perinatol 1995;19:493-501.

8. Achiron R, Weissman A, Lipitz S et al. Fetal pleural effusion: the risk of fetal trisomy. Gynecol Obstet Invest 1995;39:153-156.

9. Waller K, Chaithongwongwatthana S, Yamasmit W et al. Chromosomal abnormalities among 246 fetuses with pleural effusions detected on prenatal ultrasound examination: factors associated with an increased risk of aneuploidy. Genet Med 2005;7(6):417-421.

10. Estoff JA, Parad RB, Frigoletto FDJ, Benacerraf B. The natural history of isolated fetal hydrothorax. Ultrasound Obstet Gynecol 1992;2(3):162-5.

11. Benacerraf BR, Frigoletto FD, Wilson M. Successful midtrimester thoracentesis with analysis of the lymphocyte population in the pleural effusion. Am J Obstet Gynecol 1986;55:398-399.

12. Eddleman KA, Levine AB, Chitkara U et al. Reliability of pleural fluid lymphocyte counts in the antenatal diagnosis of congenital chylothorax. Obstet Gynecol 1991;78(3):530-532.

13. Teoh TG, Ryan G, Johnson JA et al. The role of fetal karyotyping from unconventional sources. Am J Obstet Gynecol 1996; 175: 873–877.

14. Klam S, Bigras JL, Hudon L. Predicting outcome in primary fetal hydrothorax. Fetal Diagn Ther 2005;20:366-370.

15. Yaghoobian J, Comrie M. Transitory bilateral isolated fetal pleural effusions. J Ultrasound Med 1988;7:231-232.

16. Aguirre OA, Finley BE, Ridgway LE, 3rd, Bennett TL, Cowles TA. Resolution of unilateral fetal hydrothorax with associated non-immune hydrops after intrauterine thoracentesis. Ultrasound Obstet Gynecol 1995;5:346-348.

17. Castillo RA, Devoe LD, Falls G et al. Pleural effusions and pulmonary hypoplasia. Am J Obstet Gynecol 1987;157:1252-1255.

18. Deurloo KL, Devlieger R, Lopriore E et al. Isolated fetal hydrothorax with hydrops: a systematic review of prenatal treatment options. Prenat Diagn 2007;27:893-897.

19. Rustico MA, Lanna M, Coviello D et al. Fetal pleural effusion. Prenat Diagn 2007;27:793-797.

20. Peters RE, Redwine FO, Cruikshank DP. Congenital bilateral chylothorax. Antepartum diagnosis and successful intrauterine surgical management. JAMA 1982;248:1360-1361.

21. Cardwell MS. Aspiration of fetal pleural effusions or ascites may improve neonatal resuscitation. South Med J 1996;89:177-178.

22. Gonen R, Degani S, Kugelman A, Abend M and Bader D. Intrapartum drainage of fetal pleural effusion. Prenat Diagn 1999;19:1124-1126.

23. Nicolaides KH, Azar GB. Thoraco-amniotic shunting. Fetal Diagn Ther 1990;5:153-164

24. Seeds JW, Bowes WA. Results of treatment of severe fetal hydrothorax with bilateral pleuroamniotic catheters. Obstet Gynecol 1986;68:577-580.

25. Rodeck CH, Fisk NM, Fraser DI et al. Long-term in utero drainage of fetal hydrothorax. N Engl J Med 1988; 319: 1135–1138.

26. Sepulveda W, Galindo A, Sosa A et al. Intrathoracic dislodgement of pleuro-amniotic shunt. Three case reports with long-term follow-up. Fetal Diagn Ther 2005;20:102-105.

27. Ronderos-Dumit D, Nicolini U, Vaughan J et al. Uterine-peritoneal amniotic fluid leakage: an unusual complication of intrauterine shunting. Obstet Gynecol 1991;78:913-915.

28. Picone O, Benachi A, Mandelbrot L et al. Thoracoamniotic shunting for fetal pleural effusions with hydrops. Am J Obstet Gynecol 2004;191:2047-2050.

29. Smith RP, Illanes S, Denbow ML, Soothill PW. Outcome of fetal pleural effusions treated by thoracoamniotic shunting. Ultrasound Obstet Gynecol 2005;26:63-66

30. Yinon Y, Grisaru-Granovsky S, Chaddha V, Windrim R, Seaward PGR, Kelly EN, Beresovska O, Ryan G. Perinatal outcome following fetal chest shunt insertion for pleural effusion. Ultrasound Obstet Gynecol 2010;36:58-64

31. Tanemura M, Nishikawa N, Kojima K et al. A case of successful fetal therapy for congenital chylothorax by intrapleural injection of OK-432. Ultrasound Obstet Gynecol 2001;18:371-375.

32. Okawa T, Takano Y, Fujimori K et al. A new fetal therapy for chylothorax: pleurodesis with OK-432. Ultrasound Obstet Gynecol 2001;18:376-377.

33. Jorgensen C, Brocks V, Bang J et al. Treatment of severe fetal chylothorax associated with pronounced hydrops with intrapleural injection of OK-432. Ultrasound Obstet Gynecol 2003;21:66-69.

34. Chen M, Shih JC, Wang BTet al. Fetal OK-432 pleurodesis: complete or incomplete? Ultrasound Obstet Gynecol 2005;26:791-793.

35. Nygaard U, Sundberg K, Nielsen HS et al. New treatment of early fetal chylothorax. Obstet Gynecol 2007;109:1088-1092.

36. Parra J, Amenedo M, E. Muñiz-Díaz E, Ormo F. A new successful therapy for fetal chylothorax by intrapleural injection of maternal blood. Ultrasound Obstet Gynecol 2003; 22:290-294.

Josep M Martinez Narcís Masoller: Hydrothorax (pleural effusion), Visual Encyclopedia of Ultrasound in Obstetrics and Gynecology, www.isuog.com. June 2013.

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