Neurodevelopmental outcome after antenatal therapy for fetal supraventricular tachyarrhythmia: 3‐year follow‐up of multicenter trial
Authors: Miyoshi T. , Maeno Y. , Matsuda T. , Ito Y. , Inamura N. , Kim K.‐S. , Shiraishi I. , Kurosaki K. , Ikeda T. , Sago H. ,   Collaborators,   Japan Fetal Arrhythmia Group
Published: November 2022

Objectives

Although many studies have supported the efficacy of transplacental treatment for fetal supraventricular tachyarrhythmia, the long‐term neurodevelopmental outcome after antenatal antiarrhythmic treatment is not well understood. The aim of this study was to investigate the prognosis and neurodevelopmental outcome at 36 months of corrected age and the incidence of tachyarrhythmia after birth, following protocol‐defined antenatal therapy for fetal supraventricular tachyarrhythmia.

Methods

This was a 3‐year follow‐up study of a multicenter trial that evaluated the efficacy and safety of protocol‐defined transplacental treatment for fetal supraventricular tachycardia (SVT) and atrial flutter (AFL). The primary endpoints were mortality and neurodevelopmental impairment (NDI) at 36 months of corrected age. NDI was defined as any of the following outcomes: cerebral palsy, bilateral blindness, bilateral deafness or neurodevelopmental delay. Neurodevelopmental delay was evaluated using appropriate developmental quotient scales, mainly the Kyoto Scale of Psychological Development, or examination by pediatric neurologists. The detection rate of tachyarrhythmia at birth and at 18 and 36 months of corrected age was also evaluated as the secondary endpoint. In addition, the association of NDI at 36 months with perinatal and postnatal factors was analyzed.

Results

Of 50 patients enrolled in the original trial, one withdrew consent and in two there was fetal death, leaving 47 patients available for enrollment in this follow‐up study. Of these, 45 cases were available for analysis after two infants were lost to follow‐up. The mortality rate was 2.2% (1/45) during a median follow‐up of 3.2 (range, 2.1–9.4) years. The infant died at the age of 2.1 years. Another infant had missing neurodevelopmental assessment data. In the remaining 43 infants, at 36 months of corrected age, NDI was detected in 9.3% (4/43) overall and in two of three (66.7%) cases with fetal hydrops with subcutaneous edema. Cerebral palsy was noted in two infants with severe subcutaneous edema or ascites at an early gestational age. Neurodevelopmental delay was found in two infants with severe congenital abnormalities (one with tuberous sclerosis and the other with heterotaxy syndrome). Tachyarrhythmia was present in 31.9% (15/47) cases in the neonatal period and decreased to 8.9% (4/45) and 4.5% (2/44) at 18 and 36 months of corrected age, respectively. The median ventricular rate at diagnosis was significantly higher in infants with NDI compared to those without (265 vs 229 bpm; P = 0.003). In infants with NDI, compared to those without, 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 vs 0 days; P = 0.013). Postnatal arrhythmia and physical development abnormalities were not associated with NDI.

Conclusions

This multicenter 3‐year follow‐up study is the first to demonstrate the long‐term mortality and morbidity of infants born following protocol‐defined transplacental treatment for fetal SVT and AFL. 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, in infants that have undergone antenatal treatment for fetal tachyarrhythmia and in which there are no comorbidities, the risk of NDI is low. However, in those with fetal hydrops with subcutaneous edema and/or associated severe congenital abnormalities, the risk for long‐term neurologic morbidity might be considered somewhat increased. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.