Department of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China.
Center of Clinical Mass Spectrometry, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China.
Ann Med. 2022 Dec;54(1):1150-1159. doi: 10.1080/07853890.2022.2067895.
Prediction of delivery is important for assessing due dates, providing adequate prenatal care, and suggesting appropriate interventions in preterm and post-term pregnancies. Recent metabolomic findings suggested that the temporal abundance information of metabolome can be used to predict delivery timing with high accuracy in a cohort of healthy women. However, a targeted and quantitative assay is required to further validate the clinical performance and utility of this group of metabolomic candidates in delivery prediction with a larger and independent cohort.
LC-MS/MS quantitative assays were applied to determine the plasma concentrations of four steroid metabolites, including oestriol-16-glucuronide (E3-16-Gluc), 17-alpha-hydroxyprogesterone (17-OHP), tetrahydrodeoxycorticosterone (THDOC), and androstane-3,17-diol (A-3,17-Diol) in asymptomatic women of singleton pregnancies (≥30 gestational weeks). Subsequent statistical analysis was conducted to assess the performance of the above candidates in delivery prediction.
Using LC-MS/MS, four steroids were separated and quantified in 5.5 min. The coefficients of variation (CVs) of the four analytes at the lower limit of quantification ranged from 7.9% to 14.6%, with the values greater than 0.990 in the calibration curves. Of the 585 recruited pregnant women who ended up with spontaneous delivery, 17.1% and 82.9% of the subjects delivered within and after 7 days since plasma collection, respectively. In the receiver operator curve analysis, the gestational age-adjusted area under the curve of the combined measurements of E3-16-Gluc and 17-OHP was 0.69 (95% CI: 0.60-0.76), with the sensitivity of 87.0% (95% CI: 78.8%-92.9%) and specificity of 60.2% (95% CI: 55.7%-64.6%). Moreover, the positive and the negative predictive values were 28.3%-34.0% and 93.1%-97.4% respectively for this combined panel.
We performed analytical and clinical validation of a quantitation LC-MS/MS panel for the four steroids in the plasma of pregnant women. The steroid metabolites panel of E3-16-Gluc and 17-OHP was potentially useful for predicting delivery within one week in asymptomatic women of singleton pregnancies. Key messagesA quantitative LC-MS/MS assay for determining the plasma levels of 17-OHP, THDOC, A-3,17-Diol and E3-16-Gluc was developed and validated, in order to evaluate their predictive performance in asymptomatic delivery of singleton pregnancy. The levels of E3-16-Gluc and 17-OHP were found to be significantly elevated at the time of sampling in women that delivered within one week and their combinational testing may be potentially useful in delivery prediction.
预测分娩对评估预产期、提供充分的产前护理以及在早产和过期妊娠中建议适当的干预措施非常重要。最近的代谢组学研究结果表明，代谢组的时间丰度信息可以用于预测健康女性队列的分娩时间，具有很高的准确性。然而，需要进行靶向和定量检测，以进一步验证这组代谢组候选物在具有更大和独立队列的分娩预测中的临床性能和实用性。
应用 LC-MS/MS 定量测定 4 种类固醇代谢物（包括雌三醇-16-葡糖苷（E3-16-Gluc）、17-羟孕酮（17-OHP）、四氢脱氧皮质酮（THDOC）和雄烷-3,17-二醇（A-3,17-Diol））在无症状的单胎妊娠（≥30 孕周）孕妇的血浆浓度。随后进行统计分析，以评估上述候选物在分娩预测中的性能。
使用 LC-MS/MS，在 5.5 分钟内分离并定量了 4 种类固醇。4 种分析物在定量下限的变异系数（CV）为 7.9%至 14.6%，校准曲线的 r 值大于 0.990。在招募的 585 名自然分娩的孕妇中，17.1%和 82.9%的孕妇在采血后 7 天内分娩。在接受者操作特征曲线分析中，E3-16-Gluc 和 17-OHP 联合检测的校正胎龄后的曲线下面积为 0.69（95%CI：0.60-0.76），灵敏度为 87.0%（95%CI：78.8%-92.9%），特异性为 60.2%（95%CI：55.7%-64.6%）。此外，该联合检测对这一检测面板的阳性预测值和阴性预测值分别为 28.3%-34.0%和 93.1%-97.4%。
我们对孕妇血浆中 4 种类固醇的定量 LC-MS/MS 检测进行了分析和临床验证。E3-16-Gluc 和 17-OHP 的类固醇代谢物检测面板可能有助于预测无症状单胎妊娠妇女在一周内的分娩。
为了评估其在预测单胎妊娠无症状分娩中的预测性能，我们开发并验证了一种用于测定 17-OHP、THDOC、A-3,17-Diol 和 E3-16-Gluc 血浆水平的定量 LC-MS/MS 检测方法。发现 E3-16-Gluc 和 17-OHP 的水平在一周内分娩的女性中采样时明显升高，其联合检测可能在分娩预测中具有潜在用途。
