Reproductive Epidemiology Group, Murdoch Children's Research Institute, Parkville, VIC, Australia.
Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia.
BMC Pediatr. 2024 Aug 22;24(1):536. doi: 10.1186/s12887-024-05012-6.
There are no established guidelines for the follow up of infants born after a prenatal diagnosis of a genomic copy number variant (CNV), despite their increased risk of developmental issues. The aims of this study were (i) to determine the perinatal outcomes of fetuses diagnosed with and without a CNV, and (ii) to establish a population-based paediatric cohort for long term developmental follow up.
An Australian state-wide research database was screened for pregnant individuals who had a prenatal chromosomal microarray (CMA) between 2013-2019 inclusive. Following linkage to laboratory records and clinical referrer details, hospital records were manually reviewed for study eligibility. Eligible participants were mother-child pairs where the pregnancy resulted in a livebirth, the mother was able to provide informed consent in English (did not require a translator) and the mother was the primary caregiver for the child at hospital discharge after birth. Research invitations were sent by registered post at an average of six years after the prenatal diagnostic test. Statistical analysis was performed in Stata17.
Of 1832 prenatal records examined, 1364 (74.5%) mother-child pairs were eligible for recruitment into the follow up cohort. Of the 468 ineligible, 282 (60.3%) had 'no live pregnancy outcome' (209 terminations of pregnancy (TOP) and 73 miscarriages, stillbirths, and infant deaths), 157 (33.5%) required a translator, and 29 (6.2%) were excluded for other reasons. TOP rates varied by the type of fetal CNV detected: 49.3% (109/221) for pathogenic CNVs, 18.2% (58/319) for variants of uncertain significance and 3.3% (42/1292) where no clinically significant CNV was reported on CMA. Almost 77% of invitation letters were successfully delivered (1047/1364), and the subsequent participation rate in the follow up cohort was 19.2% (201/1047).
This study provides Australia's first population-based data on perinatal outcomes following prenatal diagnostic testing with CMA. The relatively high rates of pregnancy loss for those with a prenatal diagnosis of a CNV presented a challenge for establishing a paediatric cohort to examine long term outcomes. Recruiting a mother-child cohort via prenatal ascertainment is a complex and resource-intensive process, but an important step in understanding the impact of a CNV diagnosis in pregnancy and beyond.
ACTRN12620000446965p; Registered on April 6, 2020.
尽管患有基因组拷贝数变异（CNV）的婴儿存在发育问题的风险增加，但目前尚无针对此类婴儿的产前诊断后随访的既定指南。本研究的目的是：（i）确定经产前诊断患有和未患有 CNV 的胎儿的围产期结局；（ii）建立基于人群的儿科队列，以进行长期发育随访。
对 2013 年至 2019 年期间进行产前染色体微阵列（CMA）的孕妇进行了澳大利亚全州范围的研究数据库筛查。通过与实验室记录和临床转诊医生的详细信息进行链接，对医院记录进行了手动审查以确定是否符合研究条件。符合条件的参与者为妊娠导致活产的母婴对，母亲能够以英语提供知情同意（无需翻译），并且母亲在分娩后是孩子的主要照顾者。在产前诊断性检测后平均六年，通过挂号信向研究对象发送研究邀请。使用 Stata17 进行统计分析。
在检查的 1832 份产前记录中，有 1364 对（74.5%）母婴对符合招募入随访队列的条件。在 468 名不符合条件的患者中，282 名（60.3%）无“活产妊娠结局”（209 例终止妊娠（TOP），73 例流产、死产和婴儿死亡），157 名（33.5%）需要翻译，29 名（6.2%）因其他原因被排除。TOP 率因胎儿 CNV 的类型而异：致病性 CNV 为 49.3%（109/221），意义不明的变异为 18.2%（58/319），CMA 报告无临床意义的 CNV 为 3.3%（42/1292）。几乎有 77%的邀请信成功送达（1047/1364），随后的随访队列参与率为 19.2%（201/1047）。
本研究提供了澳大利亚首例基于人群的 CMA 产前诊断后围产期结局数据。对于产前诊断为 CNV 的患者，妊娠丢失率相对较高，这给建立儿科队列以检查长期结局带来了挑战。通过产前确定来招募母婴队列是一个复杂且资源密集型的过程，但这是了解妊娠和妊娠后 CNV 诊断影响的重要步骤。
ACTRN12620000446965p；于 2020 年 4 月 6 日注册。
