Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, and Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI.
Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, and Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI; Detroit Medical Center, Detroit, MI; Department of Obstetrics and Gynecology, Florida International University, Miami, FL.
Am J Obstet Gynecol. 2021 Mar;224(3):288.e1-288.e17. doi: 10.1016/j.ajog.2020.09.002. Epub 2020 Sep 9.
A sonographic short cervix (length <25 mm during midgestation) is the most powerful predictor of preterm birth. Current clinical practice assumes that the same cervical length cutoff value should apply to all women when screening for spontaneous preterm birth, yet this approach may be suboptimal.
This study aimed to (1) create a customized cervical length standard that considers relevant maternal characteristics and gestational age at sonographic examination and (2) assess whether the customization of cervical length evaluation improves the prediction of spontaneous preterm birth.
This retrospective analysis comprises a cohort of 7826 pregnant women enrolled in a longitudinal protocol between January 2006 and April 2017 at the Detroit Medical Center. Study participants met the following inclusion criteria: singleton pregnancy, ≥1 transvaginal sonographic measurements of the cervix, delivery after 20 weeks of gestation, and available relevant demographics and obstetrical history information. Data from women without a history of preterm birth or cervical surgery who delivered at term without progesterone treatment (N=5188) were used to create a customized standard of cervical length. The prediction of the primary outcome, spontaneous preterm birth at <37 weeks of gestation, was assessed in a subset of pregnancies (N=7336) that excluded cases with induced labor before 37 weeks of gestation. Area under the receiver operating characteristic curve and sensitivity at a fixed false-positive rate were calculated for screening at 20 to 23 6/7, 24 to 27 6/7, 28 to 31 6/7, and 32 to 35 6/7 weeks of gestation in asymptomatic patients. Survival analysis was used to determine which method is better at predicting imminent delivery among symptomatic women.
The median cervical length remained fundamentally unchanged until 20 weeks of gestation and subsequently decreased nonlinearly with advancing gestational age among women who delivered at term. The effects of parity and maternal weight and height on the cervical length were dependent on the gestational age at ultrasound examination (interaction, P<.05 for all). Parous women had a longer cervix than nulliparous women, and the difference increased with advancing gestation after adjusting for maternal weight and height. Similarly, maternal weight was nonlinearly associated with a longer cervix, and the effect was greater later in gestation. The sensitivity at a 10% false-positive rate for prediction of spontaneous preterm birth at <37 weeks of gestation by a short cervix ranged from 29% to 40% throughout pregnancy, yet it increased to 50%, 50%, 53%, and 54% at 20 to 23 6/7, 24 to 27 6/7, 28 to 31 6/7, and 32 to 35 6/7 weeks of gestation, respectively, for a low, customized percentile (McNemar test, P<.001 for all). When a cervical length <25 mm was compared to the customized screening at 20 to 23 6/7 weeks of gestation by using a customized percentile cutoff value that ensured the same negative likelihood ratio for both screening methods, the customized approach had a significantly higher (about double) positive likelihood ratio in predicting spontaneous preterm birth at <33, <34, <35, <36, and <37 weeks of gestation. Among symptomatic women, the difference in survival between women with a customized cervical length percentile of ≥10th and those with a customized cervical length percentile of <10th was greater than the difference in survival between women with a cervical length ≥25 mm and those with a cervical length <25 mm.
Compared to the use of a cervical length <25 mm, a customized cervical length assessment (1) identifies more women at risk of spontaneous preterm birth and (2) improves the distinction between patients at risk for impending preterm birth in those who have an episode of preterm labor.
中孕期超声检查提示宫颈短(<25mm)是预测早产的最有力指标。目前的临床实践认为,在筛查自发性早产时,所有女性都应采用相同的宫颈长度截断值,但这种方法可能并不理想。
本研究旨在(1)建立一个考虑相关母体特征和超声检查时的妊娠龄的定制宫颈长度标准,(2)评估宫颈长度评估的定制是否能改善自发性早产的预测。
本回顾性分析纳入了 2006 年 1 月至 2017 年 4 月期间在底特律医疗中心参加纵向研究方案的 7826 名孕妇。研究参与者符合以下纳入标准:单胎妊娠、至少有 1 次经阴道超声测量宫颈、妊娠 20 周后分娩、以及有可用的相关人口统计学和产科史信息。排除有早产史或宫颈手术史且在无孕激素治疗情况下足月分娩的孕妇(N=5188)的数据用于制定定制的宫颈长度标准。在排除了妊娠 37 周前因引产而分娩的病例的妊娠(N=7336)亚组中,评估了主要结局(妊娠<37 周的自发性早产)的预测。计算了在无症状患者中 20 至 23 6/7、24 至 27 6/7、28 至 31 6/7 和 32 至 35 6/7 周时筛查的受试者工作特征曲线下面积和固定假阳性率的敏感性。生存分析用于确定哪种方法更能预测有症状孕妇的即将分娩。
在足月分娩的孕妇中,宫颈长度在 20 周前基本不变,随后随妊娠龄的增加呈非线性下降。初产妇和经产妇的宫颈长度与母亲体重和身高的影响取决于超声检查时的妊娠龄(交互作用,P<0.05)。经产妇的宫颈长度长于初产妇,且在调整了母亲的体重和身高后,这种差异随妊娠龄的增加而增加。同样,母亲的体重与宫颈长度呈非线性相关,且这种影响在妊娠后期更大。在预测妊娠<37 周的自发性早产时,以 10%的假阳性率截断值,通过短宫颈预测自发性早产的敏感性在整个孕期范围为 29%至 40%,但在 20 至 23 6/7、24 至 27 6/7、28 至 31 6/7 和 32 至 35 6/7 周时,分别增加至 50%、50%、53%和 54%,这是低、定制百分位数(McNemar 检验,P<0.001)。当将宫颈长度<25mm 与 20 至 23 6/7 周的定制筛查进行比较时,采用确保两种筛查方法的阴性似然比相同的定制截断值,定制方法在预测妊娠<33、<34、<35、<36 和<37 周的自发性早产时,阳性似然比显著更高(约为两倍)。在有症状的孕妇中,定制宫颈长度百分位数≥10%的妇女与定制宫颈长度百分位数<10%的妇女之间的生存差异大于宫颈长度≥25mm 的妇女与宫颈长度<25mm 的妇女之间的生存差异。
与使用宫颈长度<25mm 相比,定制的宫颈长度评估(1)可识别出更多有自发性早产风险的女性,(2)可改善对有早产发作风险的患者的鉴别能力。