Institute of Child Health, University College London, London, UK.
Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Dev Med Child Neurol. 2022 Oct;64(10):1237-1245. doi: 10.1111/dmcn.15224. Epub 2022 Apr 2.
To examine the association between perinatal adversities and neurodevelopmental outcome in tuberous sclerosis complex (TSC).
The Tuberous Sclerosis 2000 study is a prospective, longitudinal UK study of TSC. In phase 1, mutation type, TSC family history, tuber characteristics, presence of cardiac rhabdomyomas, seizure characteristics, and intellectual ability were assessed in 125 children affected with TSC (64 females, 61 males; median age 39mo, range 4-254). In phase 2, 88 participants (49 females, 39 males; median age 148mo, range 93-323) were assessed for neurodevelopmental outcomes including intellectual ability, autism spectrum disorder, and attention-deficit/hyperactivity disorder. Perinatal histories of 88 participants with TSC and 80 unaffected siblings were collected retrospectively using the Obstetric Enquiry Schedule and coded with a modified Gillberg Optimality Scale to measure levels of perinatal adversity. Data were analysed using Mann-Whitney U tests, Spearman's rank correlation, and linear regression with robust standard errors.
Children with familial TSC experienced significantly greater perinatal adversity than unaffected siblings. Perinatal adversity was higher in children with TSC-affected mothers than those with unaffected mothers. There was no significant association between perinatal adversities and neurodevelopmental outcomes after controlling for confounders.
Maternal TSC is a significant marker of elevated perinatal risk in addition to risks incurred by fetal genotype. Pregnancies complicated by maternal or fetal TSC require higher vigilance, and mechanisms underlying increased perinatal adversity require further research.
Higher perinatal adversity is associated with familial tuberous sclerosis complex (TSC). Maternal TSC was associated with higher frequencies of several perinatal risk markers. Paternal TSC was not associated with higher levels of perinatal adversity. Perinatal adversity levels in TSC1 and TSC2 subgroups did not differ significantly. Perinatal adversities were not associated with neurodevelopmental outcomes.
探讨围产期不良经历与结节性硬化症（TSC）神经发育结局的关系。
TSC2000 研究是一项针对 TSC 的英国前瞻性纵向研究。在第 1 阶段，评估了 125 名患有 TSC 的儿童（64 名女性，61 名男性；中位年龄 39 个月，范围 4-254 个月）的突变类型、TSC 家族史、结节特征、心脏横纹肌瘤的存在、癫痫发作特征和智力。在第 2 阶段，评估了 88 名参与者（49 名女性，39 名男性；中位年龄 148 个月，范围 93-323 个月）的神经发育结局，包括智力、自闭症谱系障碍和注意缺陷多动障碍。使用产科询问表回顾性收集了 88 名 TSC 患儿及其 80 名无患病兄弟姐妹的围产期史，并使用改良 Gillberg 优化量表进行编码，以衡量围产期不良的程度。采用 Mann-Whitney U 检验、Spearman 秩相关和线性回归进行分析，采用稳健标准误差。
家族性 TSC 患儿的围产期不良经历明显多于无患病兄弟姐妹。与无患病母亲的患儿相比，患有 TSC 母亲的患儿的围产期不良经历更高。在控制混杂因素后，围产期不良与神经发育结局之间没有显著关联。
除了胎儿基因型所带来的风险外，母体 TSC 也是围产期高风险的重要标志。母体或胎儿 TSC 合并的妊娠需要更高的警惕性，围产期不良增加的机制需要进一步研究。
更高的围产期不良与家族性结节性硬化症（TSC）有关。母体 TSC 与几种围产期风险标志物的发生频率较高有关。父系 TSC 与更高的围产期不良水平无关。TSC1 和 TSC2 亚组的围产期不良水平没有显著差异。围产期不良与神经发育结局无关。
