Neurodevelopmental outcome after antenatal therapy for fetal supraventricular tachyarrhythmia: 3‐year follow‐up of multicenter trial
Neurodevelopmental outcome after antenatal therapy for fetal supraventricular tachyarrhythmia: 3‐year follow‐up of multicenter trial
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胎儿室上性心律失常产前治疗后的神经发育结局：多中心试验的 3 年随访
DOI：
10.1002/uog.26113
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发表时间：
2023
影响因子：
7.1
通讯作者：
Japan?Fetal Arrhythmia Group
中科院分区：
文献类型：
--
作者：
Miyoshi T.;Maeno Y.;Matsuda T.;Ito Y.;Inamura N.;Kim K.‐S.;Shiraishi I.;Kurosaki K.;Ikeda T.;Sago H.;Horigome H.;Yoda H.;Tsukahara S.;Teramachi Y.;Takahashi K.;Toyoshima K.;Nakai M.;Katsuragi S.;Collaborators;Japan?Fetal Arrhythmia Group
虽然许多研究支持经胎盘治疗胎儿室上性心动过速的疗效，但产前抗心律失常治疗后的长期神经发育结局尚不清楚。本研究的目的是研究36个月矫正年龄时的预后和神经发育结局以及出生后快速心律失常的发生率，遵循方案定义的产前治疗胎儿室上性快速心律失常。方法：这是一项为期3年的多中心随访研究，旨在评估方案定义的经胎盘治疗胎儿室上性心动过速（SVT）和心房扑动（AFL）的有效性和安全性。主要终点是校正年龄36个月时的死亡率和神经发育障碍（NDI）。NDI被定义为以下任何一种结果：脑瘫、双侧失明、双侧耳聋或神经发育迟缓。神经发育迟缓的评估采用适当的发育商量表，主要是京都心理发展量表，或由儿科神经科医生进行检查。出生时、矫正年龄18个月和36个月时的速性心律失常检出率也作为次要终点进行评估。此外，还分析了36月龄NDI与围生期及产后因素的关系。结果在最初的试验中有50名患者，1名患者撤回了同意，2名患者出现了胎儿死亡，剩下47名患者可纳入这项随访研究。其中，在失去两名婴儿随访后，有45例可用于分析。中位随访时间为3.2年（2.1-9.4年），死亡率为2.2%（1/45）。这名婴儿在2.1岁时死亡。另一名婴儿缺少神经发育评估数据。在其余43名婴儿中，在矫正年龄36个月时，9.3%（4/43）的婴儿检测到NDI， 3例胎儿水肿中有2例（66.7%）检测到NDI。脑瘫是注意在两个婴儿严重皮下水肿或腹水在妊娠早期。神经发育迟缓的两个婴儿发现严重的先天性异常（一个结节性硬化症，另一个异位综合征）。新生儿期有31.9%（15/47）的病例出现过速心律失常，矫正年龄18个月和36个月时分别降至8.9%（4/45）和4.5%（2/44）。诊断时NDI婴儿的中位心室率明显高于无NDI婴儿（265vs229 bpm；P= 0.003）。与未患NDI的婴儿相比，诊断时伴有皮下水肿的胎儿水肿更为常见（50.0%vs2.6%；P= 0.019），胎儿积液持续时间更长（中位数，10.5vs0天；P= 0.013）。产后心律失常和身体发育异常与NDI无关。结论：这项为期3年的多中心随访研究首次证实了经胎盘治疗胎儿SVT和AFL后出生的婴儿的长期死亡率和发病率。NDI与胎儿水肿和诊断时皮下水肿的存在以及胎儿积液持续时间较长有关。神经发育迟缓仅在有严重先天性异常的婴儿中发现。因此，在接受过胎儿心律失常产前治疗且无合并症的婴儿中，NDI的风险较低。然而，对于那些伴有皮下水肿和/或相关的严重先天性异常的胎儿水肿，可能考虑到长期神经系统疾病的风险。
ObjectivesAlthough 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.MethodsThis 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.ResultsOf 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 (265vs229 bpm;P= 0.003). In infants with NDI, compared to those without, fetal hydrops with subcutaneous edema at diagnosis was more common (50.0%vs2.6%;P= 0.019) and the duration of fetal effusion was longer (median, 10.5vs0 days;P= 0.013). Postnatal arrhythmia and physical development abnormalities were not associated with NDI.ConclusionsThis 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 …