背景:通过超声检查可以在妊娠早期发现相当比例的主要胎儿结构异常。然而,作为全国产前筛查计划的一部分,在低风险人群中进行的妊娠早期异常扫描(FTAS)的检测性能未知.FTAS的潜在好处包括早期发现胎儿畸形,为父母提供更多的生育决策时间。
目的:为了研究摄取,转诊后的测试表现和最终产前诊断的时间。
方法:在荷兰进行了一项全国性的实施研究(2021年11月至2022年11月)。FTAS由认证的超声医师使用标准协议在妊娠12+3和14+3周之间进行。如果怀疑有异常情况,则将妇女转诊到三级护理中心。Uptake,确定了检测性能和最终产前诊断的时间(从转诊到生殖决策的最终诊断/预后之间的天数).对孕早期主要先天性异常的测试性能进行了计算,如无脑和全前脑和所有诊断异常<24周妊娠。
结果:FTAS摄取为74.9%(129704/173129)。1.0%(1313/129704),有异常被怀疑,其中54.9%(n=721)在详细的孕早期诊断扫描中发现异常,44.6%(n=586)显示正常结果。在0.5%(n=6)中,发生宫内胎儿死亡。在总共721例有异常发现的患者中,332个结构异常,117个遗传异常,82个其他发现(胎儿生物测量异常,sonomarkers,胎盘/脐带异常,羊水/羊水过少)和189例有一过性发现(定义为<24周妊娠的超声发现)被发现,一个结果未知的案例。所有FTAS正常的病例中有0.9%(n=1164)在孕中期被诊断为胎儿异常。测试性能包括对妊娠早期主要先天性异常的敏感性为84.6%(126/149),对所有类型的异常的敏感性为31.6%(537/1701)。所有异常的特异性为99.2%(98055/98830);阳性预测值40.9%(537/1312);阴性预测值98.8%(98055/99219);阳性似然比40.3;阴性似然比0.7;假阳性率0.8%(775/98830)和假阴性率68.4%(1164/1701)。诊断结构异常的中位时间为20天(6-43天;中位GA163),对于遗传异常17天(8.5-27.5天;中位GA15+6周)和妊娠早期主要先天性异常9天(5-22天;中位GA14+6周)。
结论:新引入的全国FTAS在低风险人群中的表现对妊娠早期主要先天性异常具有较高的敏感性,对所有异常合并的敏感性较低。该计划伴随着1.0%的转诊率,其中59.1%涉及异常在妊娠24周前未得到确认或解决的病例。转诊病例的诊断时间约为妊娠16周。在全国产前筛查计划中评估FTAS的益处和潜在危害之间的平衡,随着时间的推移,评估该计划的有效性并考虑妇女及其伴侣的观点至关重要,以及医疗保健专业人员。
BACKGROUND: A significant proportion of major fetal structural anomalies can be detected in the first trimester by ultrasound examination. However, the test performance of the first-trimester anomaly scan performed in a low-risk population as part of a nationwide prenatal screening program is unknown. Potential benefits of the first-trimester anomaly scan include early detection of fetal anomalies, providing parents with more time for reproductive decision-making.
OBJECTIVE: To investigate the uptake, test performance, and time to a final prenatal diagnosis after referral.
METHODS: A nationwide implementation study was conducted in the Netherlands (November 2021-November 2022). The FTAS was performed between 12+3 and 14+3 weeks of gestation by certified sonographers using a standard protocol. Women were referred to a tertiary care center if anomalies were suspected. Uptake, test performance, and time to a final prenatal diagnosis (days between referral and date of final diagnosis/prognosis for reproductive decision-making) were determined. Test performance was calculated for first-trimester major congenital anomalies, such as anencephaly and holoprosencephaly and all diagnosed anomalies <24 weeks of gestation.
RESULTS: The first-trimester anomaly scan uptake was 74.9% (129,704/173,129). In 1.0% (1313/129,704), an anomaly was suspected, of which 54.9% (n=721) had abnormal findings on the detailed first-trimester diagnostic scan and 44.6% (n=586) showed normal results. In 0.5% (n=6), intrauterine fetal death occurred. In the total group of 721 cases with abnormal findings, 332 structural anomalies, 117 genetic anomalies, 82 other findings (abnormal fetal biometry, sonomarkers, placental/umbilical cord anomaly, an-/oligohydramnios), and 189 cases with transient findings (defined as ultrasound findings which resolved <24 weeks of gestation) were found, with 1 case having an unknown outcome. 0.9% (n=1164) of all cases with a normal first-trimester anomaly scan were diagnosed with a fetal anomaly in the second trimester. Test performance included a sensitivity of 84.6% (126/149) for first-trimester major congenital anomalies and 31.6% (537/1701) for all types of anomalies. Specificity for all anomalies was 99.2% (98,055/98,830); positive predictive value 40.9% (537/1312); negative predictive value 98.8% (98,055/99,219); positive likelihood ratio 40.3; negative likelihood ratio 0.7; false positive rate 0.8% (775/98,830), and false negative rate 68.4% (1164/1701). The median time to diagnosis for structural anomalies was 20 days (6-43 days; median gestational age 16+3), for genetic anomalies 17 days (8.5-27.5 days; median gestational age 15+6 weeks), and for first-trimester major congenital anomalies 9 days (5-22 days; median gestational age 14+6 weeks).
CONCLUSIONS: The performance of a newly introduced nationwide first-trimester anomaly scan in a low-risk population showed a high sensitivity for first-trimester major congenital anomalies and a lower sensitivity for all anomalies combined. The program was accompanied by a referral rate of 1.0%, of which 59.1% involved cases where anomalies were either not confirmed or resolved before 24 weeks gestation. Timing of diagnosis was around 16 weeks of gestation for referred cases. To evaluate the balance between benefits and potential harm of the first-trimester anomaly scan within a nationwide prenatal screening program, it is essential to assess the effectiveness of the program over time and to consider the perspectives of both women and their partners, as well as healthcare professionals.