双胎之一消亡导致非侵入性产前检测假阳性病例研究

False positive non-invasive prenatal testing results due to vanishing twins

目的探究双胎之一消亡导致非侵入性产前检测(non-invasive prenatal testing,NIPT)假阳性结果的原因、规律和持续时间。方法在不同孕周对1例双胎之一消亡的孕妇进行3次NIPT检测,分析消亡前后胎儿游离DNA浓度的变化以及对NIPT结果的影响。对存活胎儿进行产前诊断,并在分娩后对活产儿胎盘、纸样胎及其胎盘进行荧光原位杂交、荧光定量PCR和组织病理学分析,明确双胎及其胎盘的遗传学诊断和病理变化,同时检索双胎之一消亡导致NIPT假阳性病例8例,分析双胎之一消亡影响NIPT结果的持续时间。结果双胎之一消亡后胎儿游离DNA在孕妇外周血中短期内增多,但持续一段时间后不再影响检测结果。消亡胎儿的组织及胎盘绒毛呈现广泛退变坏死改变。结论双胎之一消亡导致NIPT假阳性的原因是异常胎儿消亡后仍持续释放胎儿游离DNA至孕妇外周血中。早、中孕期双胎之一消亡对NIPT结果的影响至少持续7~8周,但不超过12~14周。

Objective To explore the mechanism and duration of false positive results of non-invasive prenatal testing (NIPT) caused by vanishing twins. Methods To detect the variation of cell-free fetal DNA fraction before and after the fetal death and explore its influence on the results of NIPT at different gestational weeks. Prenatal diagnosis was also carried out on amniotic fluid sample derived from the survivor twin. After birth, the two placentas and papyraceous fetus were obtained to ascertain the definitive genetic diagnosis and pathologic changes through fluorescence in situ hybridization, fluorescence quantitative PCR and histopathological examination. Eight cases of vanishing twins leading to discordant NIPT results were reviewed for determining the duration of this influence. Results The vanishing twin has led to immediate flooding of cfDNA into the maternal plasma due to necrotic cytotrophoblasts, which in turn caused increased release of fetal DNA in a short time. However, this did not change the NIPT result for a period of time. The tissue and chorionic villi of perished fetus presented extensive degenerative necrosis. Conclusion The false positive NIPT result caused by vanishing twins may be attributed to continuous release of DNA fragments into the maternal plasma by the fetuses. The influence of the vanished fetuses, which may lead to discordant NIPT results, can last for at least 7-8 weeks but no more than 12-14 weeks during the first and second trimester.