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Objectives: Although many studies have supported the efficacy of transplacental treatment for fetal supraventricular tachyarrhythmias, the long-term neurodevelopmental outcome after antenatal antiarrhythmic treatment is not well understood. The aim of this study was to clarify prognosis and neurodevelopmental outcome after protocol-defined antenatal therapy for fetal supraventricular tachyarrhythmias, in addition to the incidence of tachyarrhythmias after birth.Methods: This 3-year follow-up study of a multicenter trial for fetal supraventricular tachycardia and atrial flutter evaluated the primary endpoint of mortality and neurodevelopmental impairment (NDI). NDI was defined as any of the following outcomes: cerebral palsy, bilateral blindness, bilateral deafness, or neurodevelopmental delay. The detection rate of tachyarrhythmia was also evaluated as the secondary endpoint. In addition, the correlations between NDI and perinatal factors or postnatal factors were analyzed at 36 months of corrected age.Results: Of 50 patients, the exclusions during the protocol-defined transplacental treatment were 1 patient because of withdrawal of consent and 2 patients with fetal death, leaving 47 patients available for enrollment in this follow-up study. Among these 47 neonates, 45 were available for analysis after 2 were lost to follow-up. The mortality rate was 2.2% (1/45) during a median follow-up of 3.2 years (2.1-9.4 years). Of these 45 infants, 2 dropped out, of whom 1 died at age 2.1 years, and 1 had missing neurodevelopmental assessment data. For the remaining 43 infants, at 36 months of corrected age, NDI was detected in 9.3% (4/43) of infants overall and in 2 of 3 infants of fetal hydrops with subcutaneous edema; cerebral palsy was found in 2 infants with severe subcutaneous edema or ascites at early gestational age; and neurodevelopmental delay was found in 2 infants with tuberous sclerosis or heterotaxy syndrome. Tachyarrhythmias were present in 31.9% (15/47) in the neonatal period and gradually decreased to 8.9% (4/45) and 4.5% (2/44) at 18 and 36 months of corrected age, respectively. The ventricular rate at diagnosis was significantly higher in infants with NDI than those without (median, 265 bpm vs. 229 bpm, P=0.003). In infants with NDI, fetal hydrops with subcutaneous edema at diagnosis was more common (50.0% vs. 2.6%, P=0.019), and the duration of fetal effusion was longer (median, 10.5 days vs. 0 day, P=0.013) than those without. Whereas postnatal arrhythmia and physical development abnormalities were not associated with NDI.Conclusions: Our multicenter 3-year follow-up study was the first to demonstrate the long-term mortality and morbidity of infants born with protocol-defined transplacental treatment for fetal supraventricular tachycardia and atrial flutter. NDI was associated with the presence of fetal hydrops with subcutaneous edema at diagnosis and longer duration of fetal effusion. Neurodevelopmental delay was detected only in infants with severe congenital abnormalities. Therefore, the risk of NDI was rather low in the absence of other comorbidities. The risk for long-term neurologic morbidity might be considered, especially in cases of fetal hydrops with subcutaneous edema and/or associated severe congenital abnormalities. This article is protected by copyright. All rights reserved. [ABSTRACT FROM AUTHOR]