Twin-to-twin transfusion syndrome (TTTS) is caused by unbalanced blood flow through intertwin vascular placental anastomoses and usually presents with oligohydramnios in the donor twin and polyhydramnios in the recipient1. A randomized controlled trial demonstrated that laser coagulation of placental anastomoses improves survival rate and lowers the rate of neurological handicap2. The main cause of recipient death is cardiac overload disease as a consequence of hyper volemia and systemic arterial hypertension3, 4. The NH2 (amino)-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) is a neurohormone that is synthesized mainly in the cardiomyocytes of the ventricles in response to pressure overload, volume overload or myocardial damage. Bajoria et al. established that, in TTTS, fetal plasma BNP was correlated with cardiac function in the recipient5 and that the amount of amniotic BNP was increased in the recipient pocket6. Our objective was to investigate whether the concentration of NT-proBNP in the amniotic fluid of the recipient twin would be useful for predicting perinatal outcome, including survival and the occurrence of sequelae of cardiac overload disease, in cases of TTTS undergoing treatment by laser coagulation. The ability to predict fetal outcome would be useful for parental counseling and could influence clinical management, for example by indicating selective feticide when fetal demise appears clearly unavoidable. Amniotic fluid samples were collected from the recipient sac at the start of the fetoscopic procedure in 40 consecutive cases of TTTS undergoing laser treatment (Stage I, n = 2; Stage II, n = 21; Stage III, n = 14; Stage IV, n = 3). The concentration of NT-proBNP was measured by electrochemiluminescence (Modular E170®; Roche Diagnostics, Meylan, France) and, due to the matrix effect, reliable readings were obtained in 34 out of 40 cases (four missing values for Stage II and two missing values for Stage III cases). Concentrations of this marker were analyzed in relation to the total concentration of amniotic proteins to correct for dilution associated with polyhydramnios (Modular P®; Roche Diagnostics). The overall survival rate was 77%, with at least one survivor in 86% of cases. Five neonates (recipients) presented sequelae induced by cardiac overload (pulmonary stenosis and/or hypertrophic cardiomyopathy or pulmonary hypertension). None developed subsequent complications. We observed a correlation between the amniotic concentration of NT-proBNP and severity of TTTS, according to Quintero staging (P = 0.01) (Figure 1). No correlation was demonstrated between the amniotic concentrations of NT-proBNP and overall survival rate 48 h after laser coagulation (P = 0.6), at birth (P = 0.07) or at discharge (P = 0.2), recipient survival rate at discharge (P = 0.7), or occurrence of cardiac sequelae at birth in surviving recipients (P = 0.2). Plot showing correlation between amniotic concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) and Quintero staging (○, no Doppler anomaly in recipient; ●, presence of Doppler anomalies in recipient). There were seven overlapping values for NT-ProBNP, all below 5000 ng/g, for Stage II cases. It has been suggested in the literature that the amniotic concentration of NT-proBNP could be influenced by renal function7, 8 and amniotic distension6, 9. However, we observed no correlation between the amniotic concentrations of NT-proBNP and the deepest vertical amniotic fluid pocket, and so consider that alterations in NT-proBNP concentrations were mainly a result of cardiac overload. Some investigators have demonstrated that cardiac dysfunction in the recipient twin usually normalizes within 1 month after laser treatment10. Therefore, fetal outcome could be at least partially independent from the severity of fetal blood flow imbalance, as described by Quintero staging or any other cardiac parameter, at the time of laser treatment. In conclusion, we have demonstrated that the concentration of NT-proBNP in the amniotic fluid of the recipient was correlated with the severity of TTTS according to Quintero staging but did not predict perinatal outcome after laser coagulation treatment. We would like to thank Siemens® and Roche Diagnostics® for the generous gifts of the cystatin C, β2-microglobulin and NT-proBNP assays. A. Delabaere* , G. Marceau ?, S. Kemeny ?, V. Sapin ?, S. Ughetto?, K. Coste , D. Gallot* , * Fetal Maternal Medicine Unit, CHU Clermont-Ferrand, Maternité Hôtel-Dieu, Boulevard Léon Malfreyt, 63003 Clermont-Ferrand, France, Department of Pediatrics, CHU Clermont-Ferrand, Maternité Hôtel-Dieu, Boulevard Léon Malfreyt, 63003 Clermont-Ferrand, France, UMR CNRS 6247 GReD, Clermont Université, Faculté de Médecine, France, ? Department of Biochemistry, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France, ? Department of Biostatistics, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France