PDF(Pubmed)
Abstract：
In pregnancies where the mother has glucokinase-MODY (GCK-MODY), fetal growth is determined by fetal genotype. When the fetus inherits a maternal pathogenic GCK variant, normal fetal growth is anticipated, and insulin treatment of maternal hyperglycaemia is not recommended. At present, fetal genotype is estimated from measurement of fetal abdominal circumference on ultrasound. Non-invasive prenatal testing of fetal GCK genotype (NIPT-GCK) using cell-free DNA in maternal blood has recently been developed. We aimed to compare the diagnostic accuracy of NIPT-GCK with that of ultrasound, and determine the feasibility of using NIPT-GCK to guide pregnancy management.
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.
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.
摘要：
目的：在母亲患有葡萄糖激酶-MODY（GCK-MODY）的妊娠中，胎儿生长由胎儿基因型决定。当胎儿遗传母体致病性GCK变异体时，预期胎儿生长正常，和胰岛素治疗的母亲高血糖是不推荐的。目前,根据超声测量胎儿腹围估计胎儿基因型。最近开发了使用母体血液中的无细胞DNA对胎儿GCK基因型（NIPT-GCK）进行非侵入性产前检测。我们旨在比较NIPT-GCK与超声的诊断准确性，并确定使用NIPT-GCK指导妊娠管理的可行性。
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。
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。
