在怀孕期间实施基因组检测意味着夫妇在出生前比以往任何时候都能获得更多关于孩子遗传构成的信息。由此产生的挑战之一是临床意义不明确的遗传变异的管理。这项基于人群的研究将通过对出生前有和没有基因组拷贝数变异(CNV)的儿童进行多学科队列研究,帮助缩小这一关键的知识差距。通过比较产前确定有CNV的儿童和没有CNV的儿童,我们的目标是(1)检查它们的发育,社会情绪和健康状况;(2)测量CNV的产前诊断对母亲对儿童健康的看法的影响,行为和发育;和(3)确定2年或更长时间后被重新分类为良性或致病性的产前确定的意义未知或不确定的CNV的比例。
这项研究将建立并跟踪2013-2019年在澳大利亚维多利亚州使用染色体微阵列进行产前诊断的母子对队列。12个月至7岁的儿童将使用经过验证的评估,适龄措施。主要结果指标将是韦克斯勒学龄前和初级智力量表IV(WPSSI-IV)智商得分(2.5至7岁),年龄和阶段问卷(12-30个月),和简短的幼儿社会和情绪评估(BITSEA)得分。还将进行儿科医生的临床评估。次要结果将是从Vineland适应性行为量表获得的分数,产妇产后依恋问卷,弱势儿童量表,情绪状态简介,父母能力感量表。将对≥2年后CNV的重新分类率进行描述性分析。
本研究方案描述了在使用染色体微阵列进行产前诊断测试后儿童的第一个澳大利亚队列研究。它将提供胎儿基因组变异的长期结果,以指导基于证据的产前和产后护理。这个,反过来,将为未来的努力提供信息,以减轻在怀孕期间传达基因组不确定性的负面影响。
ACTRN12620000446965p;于2020年4月6日注册。
The implementation of genomic testing in pregnancy means that couples have access to more information about their child\'s genetic make-up before birth than ever before. One of the resulting challenges is the management of genetic variations with unclear clinical significance. This population-based
study will help to close this critical knowledge gap through a multidisciplinary cohort
study of children with and without genomic copy number variants (CNVs) diagnosed before birth. By comparing children with prenatally-ascertained CNVs to children without a CNV, we aim to (1) examine their developmental, social-emotional and health status; (2) measure the impact of prenatal diagnosis of a CNV on maternal perceptions of child health, behavior and development; and (3) determine the proportion of prenatally-ascertained CNVs of unknown or uncertain significance that are reclassified as benign or pathogenic after 2 or more years.
This
study will establish and follow up a cohort of mother-child pairs who have had a prenatal diagnosis with a chromosomal microarray from 2013-2019 in the Australian state of Victoria. Children aged 12 months to 7 years will be assessed using validated, age-appropriate measures. The primary outcome measures will be the Wechsler Preschool and Primary Scale of Intelligence IV (WPSSI-IV) IQ score (2.5 to 7 year old\'s), the Ages and Stages Questionnaire (12-30 months old), and the Brief Infant- Toddler Social and Emotional Assessment (BITSEA) score. Clinical assessment by a pediatrician will also be performed. Secondary outcomes will be scores obtained from the: Vineland Adaptive Behavior Scale, Maternal Postnatal Attachment Questionnaire, the Vulnerable Child Scale, Profile of Mood States, Parent Sense of Competence Scale. A descriptive analysis of the reclassification rates of CNVs after ≥2 years will be performed.
This
study protocol describes the first Australian cohort
study following children after prenatal diagnostic testing with chromosomal microarray. It will provide long-term outcomes of fetal genomic variants to guide evidence-based pre-and postnatal care. This, in turn, will inform future efforts to mitigate the negative consequences of conveying genomic uncertainty during pregnancy.
ACTRN12620000446965p ; Registered on April 6, 2020.