Abstract：
BACKGROUND: Preeclampsia remains a major cause of maternal and fetal adverse outcomes in pregnancy; however, accurate and universally acceptable predictive tools remain elusive. We investigated whether a panel of biomarkers could improve risk prediction for preeclampsia when measured at various pregnancy time points.
METHODS: In this prospective cohort study, 192 women with first-trimester high-risk singleton pregnancies were consecutively recruited from tertiary obstetrics clinics in Montréal, Canada. Clinical information (height, pre-pregnancy weight, personal and family medical history, medication use) was collected at baseline. Blood pressure was measured and blood samples collected at each trimester to quantify soluble Fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), pregnancy-associated plasma protein A2 (PAPP-A2), PAPP-A, activin A, inhibin A, follistatin, and glycosylated fibronectin. A random-effects hierarchic logistic regression model was used to relate change in biomarker levels to incidence of preeclampsia.
RESULTS: When added to a clinical model composed of maternal age, pre-pregnancy body mass index, race, and mean arterial pressure, a positive third-trimester result for both PAPP-A2 and activin A had a better positive predictive value than the sFlt-1:PlGF ratio added to the clinical model (91.67% [95% confidence interval (CI) 78.57%-100%] vs 66.67% [57.14%-100%]), while maintaining a comparable high negative predictive value (97.69% [95% CI 95.34%-100%] vs 96.00% [92.19%-99.21%]).
CONCLUSIONS: Whereas the third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia, PAPP-A2 and activin A had both high positive and negative predictive values and therefore could serve as biomarkers to predict the occurrence (and absence) of preeclampsia; these findings will be validated in future studies.
METHODS: In this prospective cohort study, 192 women with first-trimester high-risk singleton pregnancies were consecutively recruited from tertiary obstetrics clinics in Montréal, Canada. Clinical information (height, pre-pregnancy weight, personal and family medical history, medication use) was collected at baseline. Blood pressure was measured and blood samples collected at each trimester to quantify soluble Fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), pregnancy-associated plasma protein A2 (PAPP-A2), PAPP-A, activin A, inhibin A, follistatin, and glycosylated fibronectin. A random-effects hierarchic logistic regression model was used to relate change in biomarker levels to incidence of preeclampsia.
RESULTS: When added to a clinical model composed of maternal age, pre-pregnancy body mass index, race, and mean arterial pressure, a positive third-trimester result for both PAPP-A2 and activin A had a better positive predictive value than the sFlt-1:PlGF ratio added to the clinical model (91.67% [95% confidence interval (CI) 78.57%-100%] vs 66.67% [57.14%-100%]), while maintaining a comparable high negative predictive value (97.69% [95% CI 95.34%-100%] vs 96.00% [92.19%-99.21%]).
CONCLUSIONS: Whereas the third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia, PAPP-A2 and activin A had both high positive and negative predictive values and therefore could serve as biomarkers to predict the occurrence (and absence) of preeclampsia; these findings will be validated in future studies.
摘要：
背景：先兆子痫仍然是孕妇和胎儿不良结局的主要原因；然而，准确和普遍接受的预测工具仍然难以捉摸。我们调查了一组生物标志物在不同妊娠时间点测量时是否可以改善先兆子痫的风险预测。
方法：在这项前瞻性队列研究中，从蒙特利尔的三级产科诊所连续招募了192名妊娠早期高危单胎妊娠的妇女，加拿大。临床信息（身高，孕前体重,个人和家族病史，药物使用）在基线时收集。在每三个月测量血压并收集血样以量化可溶性Fms样酪氨酸激酶1（sFlt-1），胎盘生长因子(PlGF),妊娠相关血浆蛋白A2(PAPP-A2),PAPP-A,激活素A,抑制素A,卵泡抑素,和糖基化的纤连蛋白。使用随机效应分层逻辑回归模型将生物标志物水平的变化与先兆子痫的发生率相关联。
结果：当添加到由母亲年龄组成的临床模型中时，孕前体重指数,种族,和平均动脉压，PAPP-A2和激活素A的孕晚期阳性结果比添加到临床模型的sFlt-1：PlGF比率具有更好的阳性预测值（91.67％[95％置信区间（CI）78.57％-100％]vs66.67％[57.14％-100％]），同时保持相当高的阴性预测值(97.69%[95%CI95.34%-100%]vs96.00%[92.19%-99.21%])。
结论：尽管孕晚期sFlt-1:PlGF比率可以预测子痫前期的短期不存在，PAPP-A2和激活素A具有高的阳性和阴性预测值，因此可以作为生物标志物来预测先兆子痫的发生（和不存在）；这些发现将在未来的研究中得到验证。
方法：在这项前瞻性队列研究中，从蒙特利尔的三级产科诊所连续招募了192名妊娠早期高危单胎妊娠的妇女，加拿大。临床信息（身高，孕前体重,个人和家族病史，药物使用）在基线时收集。在每三个月测量血压并收集血样以量化可溶性Fms样酪氨酸激酶1（sFlt-1），胎盘生长因子(PlGF),妊娠相关血浆蛋白A2(PAPP-A2),PAPP-A,激活素A,抑制素A,卵泡抑素,和糖基化的纤连蛋白。使用随机效应分层逻辑回归模型将生物标志物水平的变化与先兆子痫的发生率相关联。
结果：当添加到由母亲年龄组成的临床模型中时，孕前体重指数,种族,和平均动脉压，PAPP-A2和激活素A的孕晚期阳性结果比添加到临床模型的sFlt-1：PlGF比率具有更好的阳性预测值（91.67％[95％置信区间（CI）78.57％-100％]vs66.67％[57.14％-100％]），同时保持相当高的阴性预测值(97.69%[95%CI95.34%-100%]vs96.00%[92.19%-99.21%])。
结论：尽管孕晚期sFlt-1:PlGF比率可以预测子痫前期的短期不存在，PAPP-A2和激活素A具有高的阳性和阴性预测值，因此可以作为生物标志物来预测先兆子痫的发生（和不存在）；这些发现将在未来的研究中得到验证。
