Division of Neuroscience, School of Biological Sciences, The University of Manchester, UK.
Foetal Anti-Convulsant Syndrome New Zealand, Aukland, New Zealand.
Neurotoxicol Teratol. 2023 Nov-Dec;100:107292. doi: 10.1016/j.ntt.2023.107292. Epub 2023 Sep 4.
To describe the neurodevelopmental phenotype of older children and adults with a diagnosis of Fetal Valproate Spectrum Disorder (FVSD).
In this cross-sectional study, 90 caregivers were recruited and completed a series of questionnaires regarding the neurodevelopmental outcomes of 146 individuals aged 7-37 years (M = 18.1), including individuals with a formal diagnosis of FVSD (n = 99), individuals exposed to Valproate but without an FVSD diagnosis (n = 24), and individuals not exposed to Valproate (N = 23). The mean dose of valproate exposure for individuals with an FVSD diagnosis was 1470 mg/day.
Individuals with a diagnosis of FVSD showed significantly higher levels of moderate (43.4%) and severe (14.4%) cognitive impairment than other groups (p = 0.003), high levels of required formal educational support (77.6%), and poorer academic competence than individuals not exposed to Valproate (p = 0.001). Overall psychosocial problems (p = 0.02), internalising problems (p = 0.05) and attention problems (p = 0.001), but not externalising problems, were elevated in individuals with a diagnosis of FVSD. Rates of neurodevelopmental disorders, particularly autistic spectrum disorders (62.9%) and sensory problems (80.6%) are particularly central to the FVSD phenotype. There was no evidence of a statistical dose-dependent effect, possibly due to the high mean dose of exposure having a uniformly negative impact across the sample. Individuals with FVSD had required a significant number of health and child development services.
Children and young adults with a diagnosis of FVSD are at an increased risk of a range of altered neurodevelopmental outcomes, highlighting the need for a multidisciplinary approach to clinical management across the lifespan.
描述被诊断为胎儿丙戊酸谱系障碍(FVSD)的大龄儿童和成人的神经发育表型。
在这项横断面研究中,招募了 90 名照顾者,并完成了一系列关于 146 名年龄在 7-37 岁(M=18.1)个体的神经发育结果的问卷,包括有 FVSD 正式诊断的个体(n=99)、暴露于丙戊酸但无 FVSD 诊断的个体(n=24)和未暴露于丙戊酸的个体(n=23)。有 FVSD 诊断的个体丙戊酸暴露的平均剂量为 1470mg/天。
被诊断为 FVSD 的个体的认知障碍中度(43.4%)和重度(14.4%)的发生率明显高于其他组(p=0.003),需要正规教育支持的水平较高(77.6%),且学业成绩比未暴露于丙戊酸的个体差(p=0.001)。总体心理社会问题(p=0.02)、内化问题(p=0.05)和注意力问题(p=0.001),但外化问题除外,在被诊断为 FVSD 的个体中升高。神经发育障碍的发生率,特别是自闭症谱系障碍(62.9%)和感觉问题(80.6%),是 FVSD 表型的核心特征。由于样本中暴露的平均剂量高,可能会产生一致的负面影响,因此没有证据表明存在统计学上的剂量依赖性效应。有 FVSD 的个体需要大量的健康和儿童发展服务。
被诊断为 FVSD 的儿童和青少年患有一系列神经发育障碍的风险增加,这凸显了需要在整个生命周期内采用多学科方法进行临床管理。