OBSTETRICS Amniotic fluid markers of fetal cardiac dysfunction in twin-to-twin transfusion syndrome Tim Van Mieghem, MD; Elisa Doné, MD; Léonardo Gucciardo, MD; Philipp Klaritsch, MD; Karel Allegaert, MD, PhD; Rita Van Bree; Liesbeth Lewi, MD, PhD; Jan Deprest, MD, PhD OBJECTIVE: The objective of the study was to determine whether car- diac troponin T (cTnT) and natriuretic peptides can be isolated from the amniotic fluid (AF) of pregnancies complicated by twin-to-twin transfu- sion syndrome (TTTS) and whether they correlate with fetal echocardio- graphic findings and recipient survival. STUDY DESIGN: AF samples from the recipient sac were obtained in 52 TTTS cases and 16 controls. Samples were assayed for cTnT and natri- uretic peptides. Prior to fetoscopic laser therapy, 34 recipient twins un- derwent assessment of atrioventricular flow patterns, myocardial per- formance index (MPI), and precordial venous Dopplers. Fetal survival was assessed 48 hours postoperatively. RESULTS: AF B-type natriuretic peptide and cTnT levels were elevated in TTTS and correlated with functional echocardiographic findings. Postoperative recipient survival was 72% when both AF-cTnT and left ventricular MPI were increased. If 1 of both markers was normal, sur- vival was 100% (P = .046). CONCLUSION: Combining ultrasound and AF-cTnT measurements al- lows the identification of fetuses at risk of postoperative demise. Key words: echocardiography, fetal surgery, natriuretic peptide, troponin, twin-to-twin transfusion Cite this article as: Van Mieghem T, Doné E, Gucciardo L, et al. Amniotic fluid markers of fetal cardiac dysfunction in twin-to-twin transfusion syndrome. Am J Obstet Gynecol 2010;202:48.e1-7. T win-to-twin transfusion syndrome (TTTS) occurs in 9-15% of mono- chorionic diamniotic twin pregnan- cies. 1,2 The condition is associated with a specific conformation of vascular anas- tomoses on a single placenta shared by both twins. One hypothesis explaining the etiology of the disease is an intertwin transfusional imbalance with net volume shifts from 1 fetus to the other and sub- sequent deregulation of the renal 3 and placental renin-angiotensin system. 4 In some cases, this leads to cardiac decom- pensation in the recipient fetus 5-7 and to myocardial damage and cardiac remod- eling as reflected in an increased occur- rence of congenital heart disease. 8 Fetal cardiac function can be compre- hensively assessed by ultrasound, using (amongst others) precordial venous Dopplers, intracardiac Doppler assess- ment of transvalvular blood flow, the myocardial performance or Tei index, and M-mode assessment of ventricular contractility. Two retrospective studies have suggested that cardiac functional assessment may be used to predict sur- vival of the recipient. 9,10 In postnatal life, in adults with cardiac failure, prediction of survival is best when cardiac ultrasound measurements are combined with serum derived bi- omarkers. 11 The combination of cardiac troponin T (cTnT), atrial natriuretic peptide (ANP), and B- or brain-type na- triuretic peptide (BNP) is currently used because it reflects cardiac dysfunction better than either peptide alone. This is because each peptide reflects another pathophysiologic process: elevated cTnT levels are associated with cardiac muscle damage, whereas ANP and BNP are in- creased in the presence of atrial and ven- tricular stretch, respectively. In the prenatal setting, determination of these peptides on fetal plasma would require fetal blood sampling, which is in- vasive and carries a risk of procedure- related complications. Therapy of TTTS, however, inherently involves removal of redundant amniotic fluid from the re- cipient’s sac. Because this is mainly com- posed of fetal urine, it is a potential source for fetal (cardiac) biomarkers. The pres- ence of cardiac cTnT in the amniotic fluid has previously been demonstrated in a study in growth-restricted fetuses. 12 Also, in pregnancies complicated by TTTS, ANP and BNP have been identified in the amni- otic fluid. 13,14 From the Division of Woman and Child, Department of Obstetrics and Gynecology (Drs Van Mieghem, Doné, Gucciardo, Klaritsch, Lewi, and Deprest and Ms Van Bree), and the Department of Pediatrics and Neonatology (Dr Allegaert), University Hospitals Leuven, Leuven, Belgium. Presented, in part, in poster format at the 29th Annual Meeting of the Society for Maternal-Fetal Medicine, San Diego, CA, Jan. 26-31, 2009. Received April 20, 2009; revised June 7, 2009; accepted Aug. 12, 2009. Reprints not available from the authors. T.V.M. is supported by the Flemish Government through a fellowship of the Instituut voor Wetenschap en Technologie (IWT 070715). The European Commission funds fellowships of E.D. and P.K. (Marie Curie Programme MEST CT2005 019707), L.G. (EuroSTEC; LSHC-CT-2006- 037409), and L.L. (EuroTwin2Twin #QLG1-CT-2002-01632). J.D. and K.A. are supported by the Fund for Scientific Research, Flanders (Belgium) (F.W.O. Vlaanderen), with Fundamental Clinical Investigatorships (1.8.012.07.N.02 and 1.8.002.09.N, respectively). 0002-9378/$36.00 • © 2010 Mosby, Inc. All rights reserved. • doi: 10.1016/j.ajog.2009.08.013 Research www. AJOG.org 48.e1 American Journal of Obstetrics & Gynecology JANUARY 2010