We studied an international cohort of pregnant women with hyperglycaemia due to GCK-MODY. We compared the diagnostic accuracy of NIPT-GCK with that of measurement of fetal abdominal circumference at 28 weeks\' gestation (n=38) using a directly genotyped offspring sample as the reference standard. In a feasibility study, we assessed the time to result given to clinicians in 43 consecutive pregnancies affected by GCK-MODY between July 2019 and September 2021.
In terms of diagnostic accuracy, NIPT-GCK was more sensitive and specific than ultrasound in predicting fetal genotype (sensitivity 100% and specificity 96% for NIPT-GCK vs sensitivity 53% and specificity 61% for fetal abdominal circumference 75th percentile). In terms of feasibility, a valid NIPT-GCK fetal genotype (≥95% probability) was reported in all 38 pregnancies with an amenable variant and repeated samples when needed. The median time to report was 5 weeks (IQR 3-8 weeks). For the 25 samples received before 20 weeks\' gestation, results were reported at a median gestational age of 20 weeks (IQR 18-24), with 23/25 (92%) reported before 28 weeks.
Non-invasive prenatal testing of fetal genotype in GCK-MODY pregnancies is highly accurate and is capable of providing a result before the last trimester for most patients. This means that non-invasive prenatal testing of fetal genotype is the optimal approach to management of GCK-MODY pregnancies.
方法:我们研究了一个由GCK-MODY引起的高血糖孕妇的国际队列。我们使用直接基因分型的后代样本作为参考标准,将NIPT-GCK的诊断准确性与妊娠28周时胎儿腹围的测量(n=38)进行了比较。在可行性研究中,我们评估了2019年7月至2021年9月期间43例受GCK-MODY影响的连续妊娠中临床医生获得结果的时间.
结果:在诊断准确性方面,NIPT-GCK在预测胎儿基因型方面比超声更具敏感性和特异性(NIPT-GCK的敏感性为100%,特异性为96%,而胎儿腹围75百分位数的敏感性为53%,特异性为61%)。在可行性方面,在所有38例妊娠中报告了有效的NIPT-GCK胎儿基因型(≥95%概率),其变异体及需要时重复取样.中位报告时间为5周(IQR3-8周)。对于妊娠20周之前收到的25个样本,结果报告的中位胎龄为20周(IQR18-24),23/25(92%)在28周前报告。
结论:GCK-MODY妊娠胎儿基因型的非侵入性产前检测非常准确,能够在大多数患者的最后三个月之前提供结果。这意味着胎儿基因型的非侵入性产前检测是管理GCK-MODY妊娠的最佳方法。